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The Surface pH of the Intestinal Mucosa and its Significance in the Permeability of Organic Anions

  • Chapter
Pharmacology of Intestinal Permeation II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 70 / 2))

Abstract

A general principle of membrane transport which has been extensively investigated is that of the nonionic diffusion of dissociable solutes across membranes. This principle is particularly evident where no specific transport mechanism exists to accelerate their permeation. The pH of a solute-containing phase, by altering the concentration of undissociated solute available for diffusion across a membrane permeable only to the nonionised form, will alter the overall apparent rate of solute transfer. Another expression of this general principle is the pH partition hypothesis based on the central assumption that ionised forms of solutes do not permeate membranes easily, if at all, unless there is a specific transport mechanism in operation. Any pH differences across such a membrane will cause a partition of solute in a predictable manner depending on the pH of the phases and the pK a of the solute under investigation. This is well known to pharmacologists and has been experimentally substantiated on many occasions by drug elimination studies in the kidney (Milne et al. 1958; Beckett and Rowland 1964), with artificial membrane systems (Doluisio and Swintosky 1964; Samuelov et al. 1979) and in gastrointestinal membranes such as the gastric mucosa, the small bowel, colon and rectum (Shore et al. 1957; Schanker et al. 1957, 1958, Schanker 1959; Hogben et al. 1959). What is perhaps less generally realised is the fact that in the small bowel, especially in the jejunum, although the degree of ionisation and the extent of absorption parallel one another, the two parameters do not coincide.

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References

  • Alday ES, Goldsmith MS (1975) Radiotelemetic monitoring of hydrogen ion levels of small intestine. Surg Gynecol Obstet 141:549–551

    PubMed  CAS  Google Scholar 

  • Allen A (1978) Structure of gastrointestinal mucus glycoproteins and the viscous and gel-forming properties of mucus. Br Med Bull 34:28–33

    PubMed  CAS  Google Scholar 

  • Ardisson JL, Dolisi C, Grimand D, Ozon C (1973) Les possibilites d’ajustement du pH au niveau d’une anse jejunal isolee. CR Soc Biol Paris 167:1656–1661

    CAS  Google Scholar 

  • Banwell JG, Gorbach SL, Mitra R, Pierce NF (1970) Fluid and electrolyte changes in the small intestine with acute undifferentiated human diarrhoea. Gastroenterology 58:925

    Google Scholar 

  • Barnett G, Hui S, Benet LZ (1978) Effects of theophylline on salicylate transport in isolated rat jejunum. Biochim Biophys Acta 507:517–523

    CAS  Google Scholar 

  • Barry RJC, Eggenton J (1972) Ionic basis of membrane potentials of epithelial cells in rat small intestine. J Physiol 227:217–231

    PubMed  CAS  Google Scholar 

  • Barry RJC, Jackson MJ, Smyth DH (1966 a) Handling of glycerides of acetic acid by rat small intestine in vitro. J Physiol 185:667–683

    PubMed  CAS  Google Scholar 

  • Barry RJC, Jackson M J, Smyth DH (1966 b) Transfer of propionate by a rat small intestine in vitro. J Physiol 182:150–163

    PubMed  CAS  Google Scholar 

  • Barry RJC, Eggenton J, Smyth DH, Wright EM (1967) Relation between sodium concentration, electrical potential and transfer capacity of rat small intestine. J Physiol 192:647–655

    PubMed  CAS  Google Scholar 

  • Beckett AH, Rowland M (1964) Urinary excretion kinetics of amphetamine in man. J Pharm Pharmacol 17:628–639

    Google Scholar 

  • Benn A, Swan CHJ. Cooke WT, Blair JA, Matty AJ, Smith ME (1970) Effect of intraluminal pH on the absorption of pteroylmonoglutamic acid. Br med J i:148–150

    Google Scholar 

  • Berk JE, Thomas JE, Rehfuss ME (1942) The reaction and neutralising ability of the contents of the first part of the duodenum in normal dogs under fasting conditions. Am J Physiol 136:369–376

    CAS  Google Scholar 

  • Bircher J, Mann V, Carlson HC, Code CF, Rovelstad RA (1965) Intraluminal and juxtamucosal duodenal pH. Gastroenterology 48:472–477

    PubMed  CAS  Google Scholar 

  • Blair JA, Matty AJ (1974) Acid microclimate in intestinal absorption. Clin Gastroenterol 3:183–197

    PubMed  CAS  Google Scholar 

  • Blair JA, Lucas ML, Matty AJ (1972) The acidification process of the jejunum. Gut 13:321A

    Google Scholar 

  • Blair JA, Johnson IT, Matty AJ (1974) Absorption of folic acid by everted sacs of rat jejunum. J Physiol 236:653–661

    PubMed  CAS  Google Scholar 

  • Blair JA, Lucas ML, Matty AJ (1975) Acidification in the rat proximal jejunum. J Physiol 245:333–350

    PubMed  CAS  Google Scholar 

  • Blair JA, Johnson IT, Matty AJ (1976) Aspects of intestinal folate transport in the rat. J Physiol 256:197–208

    PubMed  CAS  Google Scholar 

  • Bloch R, Haberich FJ, Lorenz-Meyer H (1972) Untersuchungen zur Transportkinetik mittelkettiger Fettsäuren am Dünndarm: (in vitro und in vivo Versuche an Ratten). Pflügers Arch 335:198–212

    PubMed  CAS  Google Scholar 

  • Bolme P, Eriksson M, Stintzing G (1977) The gastrointestinal absorption of penicillin in children with suspected coeliac disease. Acta Paediatr Scand 66:573–578

    PubMed  CAS  Google Scholar 

  • Braude R, Fulford RJ, Low AG (1976) Studies on digestion and absorption in the intestine of growing pigs. Measurement of digesta and pH. Br J Nutr 36:497–510

    PubMed  CAS  Google Scholar 

  • Braybrooks MP, Barry BW, Abbs ET (1975) The effect of mucin on the bioavailabilitiy of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations. J Pharm Pharmacol 27:508–515

    PubMed  CAS  Google Scholar 

  • Bridges JW, Houston JB, Humphrey MJ, Lindup WE, Parke DV, Shillingford JS, Upshall DG (1976) Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis. J Pharm Pharmacol 28:117–126

    PubMed  CAS  Google Scholar 

  • Briseid G, Oye I, Briseid K (1977) Increased level of cAMP in the rat intestinal mucosa caused by sodium lauryl sulphate. Naunyn Schmiedebergs Arch Pharmacol 298:263–266

    PubMed  CAS  Google Scholar 

  • Brown MM, Parsons DS (1962) Observations on the changes in the potassium content of rat jejunal mucosa during absorption. Biochim Biophys Acta 59:249–251

    PubMed  CAS  Google Scholar 

  • Burgen ASV, Goldberg NJ (1962) Absorption of folic acid from the small intestine of the rat. Br J Pharmacol Chemother 19:313–320

    PubMed  CAS  Google Scholar 

  • Catala J (1975) Effet de la ligature du canal pancreatique sur le pH intestinal chez la Lapin. CR Acad Sci (Paris) 281:1991–1993

    CAS  Google Scholar 

  • Cheng SH, White A (1962) Effect of orally administered neomycin on the absorption of penicillin-V. N Engl J Med 267:1296–1297

    PubMed  CAS  Google Scholar 

  • Chowran ZT, Amaro AA (1977) Everted rat intestinal sacs as an in vitro model for assessing absorption of new drugs. J Pharm Sci 66:1249–1253

    Google Scholar 

  • Colaizzi JL, Klink PR (1969) pH-partition behaviour of teracyclines. J Pharm Sci 58:1184–1189

    PubMed  CAS  Google Scholar 

  • Cramer JA, Prestegard JH (1977) NMR studies of pH-induced transport of carboxylic acids across phospholipid membrane vesicles. Biochem Biophys Res Commun 75:295–301

    PubMed  CAS  Google Scholar 

  • Crouthamel WG, Tan GH, Dittert LW, Doluisio JT (1971) Drug absorption IV. Influence of pH on absorption kinetics of weakly acidic drugs. J Pharm Sci 60:1160–1163

    PubMed  CAS  Google Scholar 

  • Csáky TZ, Autenrieth B (1975) Transcellular and intercellular transport. In: Csáky TZ (ed) Intestinal absorption and malabsorption. Raven, New York, pp 177–185

    Google Scholar 

  • Dainty J, House CR (1966) “Unstirred layers” in frog skin. J Physiol 182:66–78

    PubMed  CAS  Google Scholar 

  • Davis AE, Pirola RC (1968) Absorption of phenoxymethyl penicillin in patients with steatorrhoea. Australas Ann Med 17:63–65

    PubMed  CAS  Google Scholar 

  • Diamond J (1966) A rapid method for determining voltage concentration relation across membranes. J Physiol 183:83–100

    PubMed  CAS  Google Scholar 

  • Dietschy JM, Westergaard H (1975) The effect of unstirred water layers on various transport processes in the intestine. In: Csáky TZ (ed) Intestinal absorption and malabsorption. Raven, New York, pp 197–207

    Google Scholar 

  • Dolisi C, Crenesse D, Ardisson JL (1979) Modification des equilibres acido-basiques par le jejunum. Experientia 35:354–357

    PubMed  CAS  Google Scholar 

  • Doluisio JT, Swintosky JV (1964) Drug partitioning II in vitro model for drug absorption. J Pharm Sci 53:597–601

    PubMed  CAS  Google Scholar 

  • Dugas MC, Ramaswamy K, Crane RK (1975) An analysis of the D-glucose influx kinetics of in vitro hamster jejunum based on considerations of the mass transfer coefficient. Biochim Biophys Acta 382:576–589

    PubMed  CAS  Google Scholar 

  • Eisborg L (1974) Folic acid: a new approach to the mechanism of its intestinal absorption. Dan Med Bull 21:1–11

    Google Scholar 

  • Faelli A, Esposito G (1971) Bicarbonate and transintestinal potential difference of the jejunum of the rat intestine incubated in vitro. In: Broda E, Locker A, Springer-Lederer H (eds) First European biophysics congress, EVIII/29, Wien Med Akad, Vienna, pp 317–321

    Google Scholar 

  • Faelli A, Garotta G (1971 a) Bicarbonati e Potenziale transepitheliale dell’intestino digiuno di ratto incubato in vitro. Nota I. Boll Soc Ital Biol Sper 47:26–29

    CAS  Google Scholar 

  • Faelli A, Garotta G (1971 b) Bicarbonati e Potenziale transepitheliale dell’intestino digiuno di ratto incubato in vitro. Nota IL Boll Soc Ital Biol Sper 47:29–32

    CAS  Google Scholar 

  • Faust RG (1962) The effect of anoxia and lithium ions on the absorption of D-glucose by the rat jejunum in vitro. Biochim Biophys Acta 60:604–614

    PubMed  CAS  Google Scholar 

  • Fordtran JS, Locklear TW (1966) Ionic constituents and osmolarity of gastric and small-intestinal fluids after eating. Am J Dig Dis 11:503–521

    PubMed  CAS  Google Scholar 

  • Foerster H, Erdlenbruch W, Mehnert H (1967) Untersuchungen über die Beeinflussung der Glukoseresorption durch verschiedene H+-Ionenkonzentrationen. Z Gesamte Exp Med 144:14–23

    CAS  Google Scholar 

  • Graham WR, Emery ES (1928) The reaction of the intestinal contents of dogs fed on different diets. J Lab Clin Med 13:1097–1108

    CAS  Google Scholar 

  • Grayzel DM, Miller EG (1927) pH concentration of intestinal contents of dog, with special reference to inorganic metabolism. Proc Soc Exp Biol Med 24:668–672

    Google Scholar 

  • Goldman R, Silman HI, Caplan SR, Kedem O, Katchalski E (1965) Papain membrane on a collodion matrix: preparation and behaviour. Science 150:758–760

    PubMed  CAS  Google Scholar 

  • Goldman R, Kedem O, Silman HI, Caplan SR, Katchalski E (1968) Papain-collodion membranes. Preparation and properties. Biochemistry 7:486–500

    PubMed  CAS  Google Scholar 

  • Halsted CH (1979) The intestinal absorption of folates. Am J Clin Nutr 32:846–855

    PubMed  CAS  Google Scholar 

  • Harms V, Stirling CE (1977) Transport of purine nucleotides and nucleosides by in vitro rabbit ileum. Am J Physiol 233:47–55

    Google Scholar 

  • Hartley GS, Roe JW (1940) Ionic concentrations at interfaces. Trans Farad Soc 36:101–109

    CAS  Google Scholar 

  • Hepner GW (1969) The absorption of pteroylglutamic (folic) acid in rats. Br J Haematol 16:241–249

    PubMed  CAS  Google Scholar 

  • Herbert V (1967) Biochemical and hematologic lesions in folic acid deficiency. J Clin Nutr 20:562–569

    CAS  Google Scholar 

  • Hicks J, Turnberg LA (1973) The influence of secretin on ion transport in the human jejunum. Gut 14:485–490

    PubMed  CAS  Google Scholar 

  • Ho NFH, Park J, Morozowich W, Higuchi WI (1976) A physical model for the simultaneous membrane transport and metabolism of drugs. J Theor Biol 61:185–193

    PubMed  CAS  Google Scholar 

  • Hogben CAM, Tocco D, Brodie BB, Schanker LS (1959) On the mechanism of intestinal absorption of drugs. J Pharmacol Exp Ther 125:275–282

    PubMed  CAS  Google Scholar 

  • Hori R, Kagimoto Y, Kamiyama K, Inui KI (1978) Effects of free fatty acids as membrane components on permeability of drugs across bilayer lipid membranes. A mechanism for intestinal absorption of acidic drugs. Biochim Biophys Acta 509:510–518

    PubMed  CAS  Google Scholar 

  • Hoyumpa AM, Nichols S, Schenker S, Wilson FA (1976) Thiamine transport in thiamine-deficient rats. Role of unstirred water layer. Biochim Biophys Acta 436:438–447

    PubMed  CAS  Google Scholar 

  • Hubel KA (1971) Effects of secretin and glucagon on intestinal transport of ions and water in the rat. Proc Soc Exp Biol Med 139:656–658

    Google Scholar 

  • Hubel KA (1973) Effect of luminal sodium concentration on bicarbonate absorption in rat jejunum. J Clin Invest 52:3172–3179

    PubMed  CAS  Google Scholar 

  • Hubel KA (1976) Intestinal ion transport: effect of norepinephrine, pilocarpine and atropine. Am J Physiol 231:252–257

    PubMed  CAS  Google Scholar 

  • Hubel KA (1977) Effects of bethanechol on intestinal ion transport in the rat. Proc Soc Exp Biol Med 154:41–44

    PubMed  CAS  Google Scholar 

  • Izak G, Galevski K, Grossowicz N, Jablonska M, Rachmilewitz M (1972) Studies on folic acid absorption in the rat II. The absorption of crystalline pteroylmonoglutamic acid from selected small intestine segments. Dig Dis Sci 17:599–602

    CAS  Google Scholar 

  • Jackson MJ (1968) Regional variation of propionate transport in rat small intestine. Life Sci 7:517–523

    PubMed  CAS  Google Scholar 

  • Jackson MJ (1975) Transport of short chain fatty acids. In: Smyth DH (ed) Intestinal absorption: biomembranes. Biomembranes, vol 4B. Plenum, London, pp 673–711

    Google Scholar 

  • Jackson MJ (1977) Epithelial transport of weak-electrolytes. Properties of a three compartment system. J Theor Biol 64:771–788

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Airall A (1978) Transport of heterocyclic acids across rat small intestine in vitro. J Membr Biol 38:255–269

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Kutcher LM (1977) The three compartment system for transport of weak electrolytes in the small intestine. In: Kramer M, Lauterbach F (eds) Intestinal permeation. Excerpta Medica, Amsterdam, pp 65–73

    Google Scholar 

  • Jackson MJ, Morgan BN (1975) Relations of weak electrolyte transport and acid-base metabolism in rat small intestine in vitro. Am J Physiol 228:482–487

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Smyth DH (1968) Role of sodium in the intestinal active transport of organic solutes. Nature 219:388–389

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Shiau YF, Bane S, Fox M (1974) Intestinal transport of weak-electrolytes; evidence in favour of a three compartment system. J Gen Physiol 63:187–213

    PubMed  CAS  Google Scholar 

  • Jackson MJ, Williamson AM, Dombrowski WA, Garner DE (1978) Intestinal transport of weak electrolytes: determinants of influx at the luminal surface. J Gen Physiol 71:301–327

    PubMed  CAS  Google Scholar 

  • Jennich RI, Ralston ML (1979) Fitting nonlinear models to data. Annu Rev Biophys Bioeng 8:195–238

    Google Scholar 

  • Kakemi K, Arita T, Hori R, Konishi R, Nishimura K, Matsui H, Nishimura T (1969) Absorption and excretion of drugs XXXIV. An aspect of drug mechanism of drug absorption from the intestinal tract in rats. Chem Pharm Bull 17:255–261

    PubMed  CAS  Google Scholar 

  • Kesavan V, Noronha JM (1971) Effect of X-irradiation on the absorption of naturally occurring folates. Int J Radia Biol 19:205–214

    CAS  Google Scholar 

  • Kesavan V, Noronha JM (1978) An ATPase dependent radiosensitive acidic microclimate essential for intestinal folate transport. J Physiol 280:1–7

    PubMed  CAS  Google Scholar 

  • King CR, Schloerb PR (1972) Gastric juice neutralisation in the duodenum. Surg Gynecol Obstet 135:22–28

    PubMed  CAS  Google Scholar 

  • Kitis G, Lucas ML, Schneider RE, Bishop H, Sargent A, Blair JA, Allan RN (1979) Jejunal acid microclimate and its effects on absorption of folic acid and propanolol. Gut 20:438A

    Google Scholar 

  • Kitis G, Lucas ML, Bishop H, Sargent A, Schneider RE, Blair JA, Allan RN (1982) Surface pH and drug absorption in coeliac disease. Clin Sc Mol Med 63:373–380

    CAS  Google Scholar 

  • Koizumi T, Arita T, Kakemi K (1964) Absorption and excretion of drugs. XX. Some pharmacokinetic aspects of absorption and excretion of sulphonamides (2). Absorption from the small intestine. Chem Pharm Bull 12:421–427

    PubMed  CAS  Google Scholar 

  • Kramer P, Ingelfinger FJ (1961) The effect of specific foods and water loading on the small intestinal function of ileostomised human subjects. Gastroenterology 40:683A

    Google Scholar 

  • Lamers JMJ (1975) Some characteristics of monocarboxylic acid transfer across the cell membrane of epithelial cells from rat small intestine. Biochim Biophys Acta 413:265–276

    CAS  Google Scholar 

  • Lamers JMJ, Hulsman WC (1975) Inhibition of pyruvate transport by fatty acids in isolated cells from rat small intestine. Biochim Biophys Acta 394:31–45

    PubMed  CAS  Google Scholar 

  • Lauterbach F (1977) Intestinal secretion of organic ions and drugs. In: Kramer M, Lauterbach F (eds) Intestinal permeation. Excerpta Medica, Amsterdam, pp 173–166

    Google Scholar 

  • Lei FH, Lucas ML, Blair JA (1977) The influence of pH low sodium ion concentration and methotrexate on jejunal surface pH: a model for folic acid transfer. Biochem Soc Trans 5:149–152

    PubMed  CAS  Google Scholar 

  • Lepot A, Banwell JG (1976) The Syrian hamster: a reproducible model for studying changes in intestinal fluid secretion in response to enterotoxin challenge. Infect Immun 14:1167–1171

    PubMed  CAS  Google Scholar 

  • Lerche D (1976) Temporal and local concentration changes in diffusion layers at cellulose membranes due to concentration differences between solutions on both sides of the membrane. J Membr Biol 27:193–205

    PubMed  CAS  Google Scholar 

  • Levin RJ (1979) Fundamental concepts of structure and function of the intestinal epithelium. In: Duthie HL., Wormsley KG (eds) Scientific basis of gastroenterology. Livingstone, Edinburgh, pp 308–338

    Google Scholar 

  • Levin RJ, Syme G (1975) Thyroid control of small intestinal oxygen consumption and influence of sodium ions, oxygen tension, glucose and anaesthesia. J Physiol 245:271–287

    PubMed  CAS  Google Scholar 

  • Lovering EG, Black DB (1974) Drug permeation through membranes III. Effect of pH and various substances on permeation of phenylbutazone through everted rat intestine and polydimethylsiloxane. J Pharm Sci 63:671–676

    PubMed  CAS  Google Scholar 

  • Lucas ML (1974) Acidification in the rat proximal jejunum. PhD thesis, University of Aston in Birmingham

    Google Scholar 

  • Lucas ML (1976) The association between acidification and electrogenic events in rat proximal jejunum. J Physiol 257:645–662

    PubMed  CAS  Google Scholar 

  • Lucas ML, Blair JA (1978) The magnitude and distribution of the acid microclimate in proximal jejunum and its relation to luminal acidification. Proc R Soc Lond, 200:27–41

    PubMed  CAS  Google Scholar 

  • Lucas ML, Schneider W, Haberich F J, Blair JA (1975) Direct measurement by pH-micro-electrode of the pH-microclimate in rat proximal jejunum. Proc R Soc Lond, 192:39–48

    PubMed  CAS  Google Scholar 

  • Lucas ML, Blair JA, Cooper BT, Cooke WT (1976) Relationship of the acid microclimate in rat and human intestine to malabsorption. Biochem Soc Trans 4:154–156

    PubMed  CAS  Google Scholar 

  • Lucas ML, Cooper BT, Lei FH, Holmes GKT, Johnson IT, Blair JA, Cooke WT (1978 a) Surface pH in Crohn’s and coeliac disease: a model for folic acid absorption. Gut 19:735–742

    PubMed  CAS  Google Scholar 

  • Lucas ML, Swanston SK, Lei FH, Mangkornthong P, Blair JA (1978 b) Effect of ethanol, diphenylhydantoin, methotrexate and low sodium ion concentration on jejunal surface pH and folic acid transfer in the rat. Biochem Soc Trans 6:297–298

    PubMed  CAS  Google Scholar 

  • Lucas ML, Cooper BT, Dunne WT, Cooke WT, Allan RN, Blair JA (1979) IRCS Med Sci 8:181

    Google Scholar 

  • Lucas ML, Lei FH, Blair JA (1980) The influence of buffer pH, glucose and sodium ion concentration on the acid microclimate in rat proximal jejunum in vitro. Pflügers Archiv 385:137–142

    PubMed  CAS  Google Scholar 

  • Lukie BE, Westergaard H, Dietschy JM (1974) Validation of a chamber that allows measurements of both tissue uptake rates and unstirred layer thicknesses in the intestine under conditions of controlled stirring. Gastroenterology 67:652–661

    PubMed  CAS  Google Scholar 

  • Lyon J, Crane RK (1966) Studies on transmural potentials in vitro in relation to intestinal absorption. I. Apparent Michaelis constants for Na+ dependent sugar transport. Biochim Biophys Acta 112:278–291

    PubMed  CAS  Google Scholar 

  • MacKenzie JF, Russell RI (1976) The effect of pH on folic acid absorption in man. Clin Sci Mol Med 51:363–368

    PubMed  CAS  Google Scholar 

  • Maggi P, Brue F, Brousoulle B, Bensimon E, Peres G (1970) Les tensions d’O2 et de CO2 au niveau de l’épithelium du Rat au cours d’expériences d’absorption in vivo. Effets del’hyperoxie et de l’hypercapnie. C R Soc Biol Paris 164:2285–2287

    PubMed  CAS  Google Scholar 

  • Malenkov AG, Melikyants AG (1977) Ion permeability and strength of cell contacts. J Membr Biol 36:97–113

    PubMed  CAS  Google Scholar 

  • Mattila MJ, Jussila J, Takki S (1973) Drug absorption in patients with intestinal villous atrophy. Arzneim Forsch 23:583–585

    CAS  Google Scholar 

  • McGee L, Hastings AB (1942) The carbon dioxide tension and acid base balance of jejunal secretions in man. J Biol Chem 142:893–904

    CAS  Google Scholar 

  • McHardy GJR, Parsons DS (1956) The absorption of inorganic phosphate from the small intestine of the rat. Q J Exp Physiol 41:399–409

    Google Scholar 

  • McKenny JR (1971) Electrolyte fluxes and electrical potentials in isolated rat intestine. In: Skoryna SC, Waldron-Edward D (eds) Intestinal absorption of metal ions, trace elements and radionuclides. Pergamon, Oxford, pp 81–100

    Google Scholar 

  • McRobert GR (1928) Observations on the hydrogen ion concentration of the alimentary canal of the albino rat. Ind J Med Res 16:545–552

    CAS  Google Scholar 

  • Meldrum SJ, Watson BW, Riddle HC, Bown RL, Sladen G (1972) pH-profile of gut as measured by radiotelemetry capsule. Br Med J 8 april:104–106

    Google Scholar 

  • Milne MD, Scribner BH, Crawford MA (1958) Nonionic diffusion and the excretion of weak acids and bases. Am J Med 24:709–729

    PubMed  CAS  Google Scholar 

  • Moore WJ (1965) Physical chemistry 4th edn. Longmans, London, p 766

    Google Scholar 

  • Morishita T, Yata N, Kamada A, Aoki M (1971) Studies on absorption of drugs VI. Effects of buffer component on the absorption of drugs. Chem Pharm Bull 19:1925–1928

    PubMed  CAS  Google Scholar 

  • Mukerji K, Saxena KC, Misra PK, Ghatak S (1977) Human ascaris — purification of chymotrypsin inhibitor and properties of partially purified chymotrypsin and trypsin inhibitors. Ind J Med Res 66:745–755

    CAS  Google Scholar 

  • Murer H, Hopfer U, Kinne R (1976) Sodium/proton antiport in brush border membrane vesicles isolated from rat small intestine and kidney. Biochem J 154:597–604

    PubMed  CAS  Google Scholar 

  • Nakamura J, Shima K, Kimura T, Muranishi S, Sezaki H (1978) Role of intestinal mucus in the absorption of quinine and water soluble dyes from the rat small intestine. Chem Pharm Bull 26:857–863

    PubMed  CAS  Google Scholar 

  • Naupert C, Rommel K (1975) Absorption of short and medium chain fatty acids in the jejunum of the rat. Z Klin Chem Klin Biochem 13:553–562

    PubMed  CAS  Google Scholar 

  • Nelson JD, Shelton S, Kumiesz HT, Haltalin KC (1972) Absorption of ampicillin and nalidixic acid by infants and children with acute shigellosis. Clin Pharmacol Ther 13:879–886

    PubMed  CAS  Google Scholar 

  • Nogami H, Hanano M, Aruga M (1966) Studies on absorption and excretion of drugs. VI. Effects of cations and 2,4-dinitrophenol on the transport of sulphonamides through the small intestine of rat. Chem Pharm Bull 14:166–173

    PubMed  CAS  Google Scholar 

  • Nogami H, Matsuzawa T (1961) Studies on absorption and excretion of drugs. I. Kinetics of penetration of acidic drug, salicylic acid through the intestinal barrier in vitro. Chem Pharm Bull 9:532–540

    CAS  Google Scholar 

  • Olinger EJ, Bertino JR, Binder HJ (1973) Intestinal folate absorption II. J Clin Invest 52:2138–2145

    PubMed  CAS  Google Scholar 

  • Oser BL (1928) The intestinal pH in experimental rickets. J Biol Chem 80:487–497

    CAS  Google Scholar 

  • Parsons DS (1956) The absorption of bicarbonate saline solutions by the small intestine and colon of the white rat. Q J Exp Physiol 41:411–420

    Google Scholar 

  • Parsons RL (1977) Drug absorption in gastrointestinal disease with particular reference to malabsorption syndromes. Clin Pharmacokinet 2:45–60

    PubMed  CAS  Google Scholar 

  • Parsons RL, Jusko WJ, Young JM (1976 a) Pharmacokinetics of antibiotic absorption in coeliac disease. J Antimicrob Chemother 2:214–215

    PubMed  CAS  Google Scholar 

  • Parsons RL, Kaye CM, Raymond K, Trounce JR, Turner P (1976 b) Absorption of propranolol and practolol in coeliac disease. Gut 17:139–143

    PubMed  CAS  Google Scholar 

  • Podesta RB, Mettrick DF (1974) The effect of bicarbonate and acidification on water and electrolyte absorption by the intestine of normal and infected (Hymenolepsis diminuta: Cestoda) rats. Dig Dis Sci 19:725–735

    CAS  Google Scholar 

  • Podesta RB, Mettrick DF (1977 a) HCO3 transport in rat jejunum: relationship to NaCl and H2O transport in vivo. Am J Physiol 232:62–68

    Google Scholar 

  • Podesta RB, Mettrick DF (1977 b) Bicarbonate and hydrogen ion secretion in rat ileum in vivo. Am J Physiol 232:574–579

    Google Scholar 

  • Poe M (1977) Acidic dissociation constants of folic acid, dihydrofolic acid and methotrexate. J Biol Chem 252:3724–3728

    PubMed  CAS  Google Scholar 

  • Poigler H, Schletter Ch (1979) Interactions of cations and chelators with the intestinal absorption of tetracycline. Naunyn Schmiedebergs Arch Pharmacol 306:89–92

    Google Scholar 

  • Ponz F, Larralde J (1950) La absorcion de azucars en funcion del pH intestinal. Rev Esp Fisiol 6:255–269

    PubMed  CAS  Google Scholar 

  • Porte D, Entenman C (1965) Fatty acid metabolism in segments of rat intestine. Am J Physiol 208:607–614

    PubMed  CAS  Google Scholar 

  • Portnoy HD (1967) The construction of glass electrodes. In: Eisenman G (ed) Glass electrodes for hydrogen and other cations. Arnold, London, pp 248–250

    Google Scholar 

  • Powell DW, Solberg LI, Plotkin GR, Catlin DH, Maenza RM, Formal SB (1971) Experimental diarrhea III. Bicarbonate transport in rat salmonella enterocolitis. Gastroenterology 60:1076–1087

    PubMed  CAS  Google Scholar 

  • Read NW, Barber DC, Levin RJ, Holdsworth CD (1977) Unstirred layer and kinetics of electrogenic absorption in the human jejunum in situ. Gut 18:865–876

    PubMed  CAS  Google Scholar 

  • Redman T, Willimot SG, Wokes F (1927) LXXXIII. The pH of the gastrointestinal tract of certain rodents used in feeding experiments and its possible significance in rickets. Biochem J 21:589–605

    PubMed  CAS  Google Scholar 

  • Remke H, Luppa D, Muller F (1975) Monosaccharidabhängiger K + -Einfluß über die Mikrovillimembran des Jéjunums der Ratte. Acta Biol Med Ger 34:1567–1572

    PubMed  CAS  Google Scholar 

  • Robinson CS (1935) The hydrogen ion concentration of the contents of the small intestine. J Biol Chem 108:403–408

    CAS  Google Scholar 

  • Robinson CS, Luckey H, Mills H (1942) Factors affecting the hydrogen ion concentration of the contents of the small intestine. J Biol Chem 147:175–181

    Google Scholar 

  • Robinson JWL (1972) Experimental intestinal malabsorption states and their relation to clinical syndromes. Klin Wochenschr 50:173–185

    PubMed  CAS  Google Scholar 

  • Roos A (1965) Intracellular pH and intracellular buffering power of the cat brain. Am J Physiol 209:1233–1246

    PubMed  CAS  Google Scholar 

  • Russell RM, Dhar JG, Dutta SK, Rosenberg IH (1979) Influence of the intraluminal pH on folate absorption: studies in control subjects and in patients with pancreatic insufficiency. J Lab Clin Med 93:428–436

    PubMed  CAS  Google Scholar 

  • Sallee VL, Dietschy JM (1973) Determinants of intestinal mucosal uptake of short and medium chain fatty acids and alcohols. J Lipid Res 14:475–484

    PubMed  CAS  Google Scholar 

  • Sallee VL, Wilson FA, Dietschy JM (1972) Determination of unidirectional uptake rates for lipids across the intestinal brush border. J Lipid Res 13:184–192

    PubMed  CAS  Google Scholar 

  • Samuelov Y, Donbrow M, Friedman M (1979) Effect of pH on salicylic acid permeation through ethyl cellulose PEG 4,000 films. J Pharm Pharmacol 31:120–121

    PubMed  CAS  Google Scholar 

  • Schanker LS (1959) Absorption of drugs from the rat colon. J Pharm Exp Ther 126:283–290

    CAS  Google Scholar 

  • Schanker LS, Less MJ (1977) Lung pH and pulmonary absorption of nonvolatile drugs in the rat. Drug Metab Dispos 5:174–178

    PubMed  CAS  Google Scholar 

  • Schanker LS, Shore PA, Brodie BB, Hogben CAM (1957) Absorption of drugs from the stomach. J Pharm Exp Ther 120:528–545

    CAS  Google Scholar 

  • Schanker LS, Tocco D, Brodie BB, Hogben CAM (1958) Absorption of drugs from rat small intestine. J Pharm Exp Ther 123:81–88

    CAS  Google Scholar 

  • Schmitt MG, Soergel KH, Wood CM, Steff JJ (1977) Absorption of short-chain fatty acids from the human ileum. Am J Dig Dis 22:340–347

    PubMed  CAS  Google Scholar 

  • Schneider RE, Babb J, Bishop H, Mitchard M, Hoare AM, Hawkins CF (1976) Plasma levels of propranolol in treated patients with coeliac disease and patients with Crohn’s disease. Br Med J 2 oct: 794–795

    PubMed  CAS  Google Scholar 

  • Schneider RE, Bishop H, Hawkins CF, Kitis G (1979) Drug binding to α-glycoprotein. Lancet 10 March: 554

    Google Scholar 

  • Schnell RC, Miya T (1970) Altered absorption of drugs from the rat small intestine by carbonic anhydrase inhibition. J Pharm Exp Ther 174:177–184

    CAS  Google Scholar 

  • Schuerman W, Turner P (1978) A membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the β-blocking drugs atenolol and propranolol. J Pharm Pharmacol 30:137–147

    Google Scholar 

  • Scott D (1965) Factors influencing the secretion and absorption of calcium and magnesium in the small intestine of the sheep. Q J Exp Physiol 50:313–329

    Google Scholar 

  • Seebald H, Forth W (1977) Absorption of 14C-bumadizone — Ca and 14C-phenylbutazone in isolated intestinal segments in vitro and tied off gastrointestinal sections in vivo of rats and guinea pigs. Drug Res 27:624–635

    CAS  Google Scholar 

  • Selhub J, Brin H, Grossowicz N (1973) Uptake and reduction of radioactive folate by everted sacs of rat small intestine. Eur J Biochem 33:433–438

    PubMed  CAS  Google Scholar 

  • Shore PA, Brodie BB, Hogben CAM (1957) The gastric secretion of drugs: a pH partition hypothesis. J Pharm Exp Ther 120:361–369

    Google Scholar 

  • Silk DBA (1979) Intestinal absorption of carbohydrate and protein in man. In: Crane RK (ed) Gastrointestinal physiology ed. III. International reviews in physiology. MTP Press, Lancaster, pp 151–204

    Google Scholar 

  • Sladen G, Dawson AM (1968) Effect of bicarbonate on sodium absorption by the human jejunum. Nature 218:267–268

    PubMed  CAS  Google Scholar 

  • Smith ME (1973) The uptake of pteroylglutamic acid by the rat jejunum. Biochim Biophys Acta 298:124–129

    PubMed  CAS  Google Scholar 

  • Smith ME, Matty AJ, Blair JA (1970) The transport of folic acid across the small intestine of the rat. Biochim Biophys Acta 219:37–46

    PubMed  CAS  Google Scholar 

  • Smolen V (1973) Misconceptions and thermodynamic untenability of deviations from pH-partition hypothesis. J Pharm Sci 62:77–79

    PubMed  CAS  Google Scholar 

  • Smyth DH, Taylor CB (1958) Intestinal transfer of short chain fatty acids in vitro. J Physiol 141:73–80

    PubMed  CAS  Google Scholar 

  • Soergel KH (1971) Flow measurements of test meals and fasting contents in the human small intestine. In: Demling L, Ottenjahn R (eds) Gastrointestinal motility. Thieme, Stuttgart, pp 81–96

    Google Scholar 

  • Stehle RH, Higuchi WI (1972) In vitro model for transport of solutes in a three phase system. I. Theoretical principles. J Pharm Sci 61:1922–1930

    PubMed  CAS  Google Scholar 

  • Steinmetz PR (1974) Cellular mechanism of urinary acidification. Physiol Rev 54:890–956

    PubMed  CAS  Google Scholar 

  • Stevens CE, Dobson A, Mammano JH (1969) A transepithelial pump for weak electrolytes. Am J Physiol 216:983–987

    PubMed  CAS  Google Scholar 

  • Strombeck DR (1972) The production of intestinal fluid by cholera toxin in the rat. Proc Soc Exp Biol Med 140:297–303

    PubMed  CAS  Google Scholar 

  • Swales JD, Tange JD, Wrong O (1970) The influence of pH, bicarbonate and hypertonicity on the absorption of ammonia from the rat intestine. Clin Sci 39:769–779

    PubMed  CAS  Google Scholar 

  • Swanston SK, Blair JA, Matty AJ, Cooper BT, Cooke WT (1977) Changes in the jejunal glycocalyx and their relationship to intestinal malabsorption. Trans Biochem Soc 5:152A

    Google Scholar 

  • Takasaka M (1978) Volatile fatty acids and pH in the gastrointestinal contents of normal and shigella infected monkeys. Jpn J Vet Res 40:343–348

    CAS  Google Scholar 

  • Takasugi N, Nakamura K, Hayashi T, Tsunakawa N, Takeya Y (1968) Studies on gastrointestinal absorption of nalidixic acid. Chem Pharm Bull 16:13–16

    PubMed  CAS  Google Scholar 

  • Teorell T (1937) Kinetics of distribution of substances administered to the body. I. Extra-vascular modes of administration. Arch Int Pharmacol 57:205–225

    CAS  Google Scholar 

  • Thomson ABR, Dietschy JM (1977) Derivation of the equations that describe the effects of unstirred water layers on the kinetic parameters of active transport processes in the intestine. J Theor Biol 64:277–294

    PubMed  CAS  Google Scholar 

  • Tripp JH, Manning JA, Muller DPR, Walker-Smith JA, O’Donoghue DP, Kumar PJ, Harries JT (1977) Mucosal adenylate cyclase and sodium-potassium stimulated adenosine triphosphatase in jejunal biopsies of adults and children with coeliac disease. In: McNichol B, McCarthy CF, Fottrell PF (eds) Perspectives in coeliac disease. MTP Press, London, pp 461–470

    Google Scholar 

  • Turnberg LA (1977) Intestinal transport of salt and water. Clin Sci Mol Med 54:337–348

    Google Scholar 

  • Turnberg LA, Fordtran JS, Carter NW, Rector FC (1970 a) Mechanism of bicarbonate absorption and its relationship to sodium transport in the human jejunum. J Clin Invest 49:548–556

    PubMed  CAS  Google Scholar 

  • Turnberg LA, Bieberdorf FA, Morawski SG, Fordtran JS (1970 b) Interrelationships of chloride, bicarbonate, sodium and hydrogen ion transport in the human ileum. J Clin Invest 49:557–567

    PubMed  CAS  Google Scholar 

  • Turner RH, Mehta CS, Benet LZ (1970) Apparent directional permeability coefficients for drug ions: in vitro intestinal perfusion studies. J Pharm Sci 59:590–595

    PubMed  CAS  Google Scholar 

  • Ugolev AM, Laey P (1973) Membrane digestion: a concept of enzymic hydrolysis on cell membranes. Biochim Biophys Acta 300:105–128

    PubMed  CAS  Google Scholar 

  • Vaz WLC, Nicksch A, Jaehnig F (1978) Electrostatic interactions at charged lipid membranes. Measurement of surface pH with flourescent lipid pH indicators. Eur J Biochem 83:299–305

    PubMed  CAS  Google Scholar 

  • Venho VMK (1976) Drug absorption from the small intestine of the triparanol-treated rat in situ. Acta Pharmacol Toxicol 39:321–330

    CAS  Google Scholar 

  • Venkataraman S, Horbett TA, Hoffmann S (1977) The reactivity of α-chymotrypsin immobilised on radiation-grafted hydrogel surfaces. J Biomed Mater Res 8:111–123

    Google Scholar 

  • Waddell WJ (1975) Role of membrane-bound enzymes in biological transport. In: Csáky TZ (ed) Intestinal absorption and malabsorption. Raven, New York, pp 37–44

    Google Scholar 

  • Wagner JG, Sedman AJ (1973) Quantitation of rate of gastrointestinal and buccal absorption of acidic and basic drugs based on extraction theory. J Pharmacokinet Biopharm 1:23–50

    CAS  Google Scholar 

  • Waldron-Edward D (1971) Effects of pH and counter-ion on absorption of metal ions. In: Skoryna SC, Waldron-Edward D (eds) Intestinal absorption of metal ions, trace elements and radionuclides. Pergamon, Oxford, pp 373–382

    Google Scholar 

  • White JF (1976) Intracellular potassium activities in Amphiuma small intestine. Am J Physiol 231:1214–1219

    PubMed  CAS  Google Scholar 

  • White JF (1977) Activity of chloride in absorptive cells of amphiuma small intestine. Am J Physiol 232:553–559

    Google Scholar 

  • Wilson TH (1953) Lactate and hydrogen ion gradients developed across rat intestine in vitro. Biochim Biophys Acta 11:448–449

    PubMed  CAS  Google Scholar 

  • Wilson TH (1956) Concentration gradients of lactate, hydrogen and some other ions across the intestine in vitro. Biochem J 56:521–527

    Google Scholar 

  • Wilson TH, Kazyak L (1957) Acid base changes across the wall of hamster and rat intestine. Biochim Biophys Acta 24:124–132

    PubMed  CAS  Google Scholar 

  • Wingate DL, Krag E, Mekhjian JS, Phillips SF (1973) Relationships between ion and water movement in human jejunum, ileum and colon during perfusion with bile acids. Clin Sci Mol Med 45:593–606

    PubMed  CAS  Google Scholar 

  • Winne D (1973) Unstirred layer, source of biased Michaelis constant in membrane transport. Biochim Biophys Acta 298:27–31

    PubMed  CAS  Google Scholar 

  • Winne D (1977) Shift of pH-absorption curves. J Pharmacokinet Biopharm 5:53–94

    PubMed  CAS  Google Scholar 

  • Winne D (1978) Dependence of intestinal absorption in vivo on the unstirred layer. Naunyn Schmiedebergs Arch Pharmacol 304:175–181

    PubMed  CAS  Google Scholar 

  • Zeuthen T (1978) Intra- and extra-cellular pH of absorptive epithelia measured with micro-electrodes. Gastroenterol Clin Biol 3:334A

    Google Scholar 

  • Zeuthen T, Monge C (1975) Intra- and extra-cellular gradients of electrical potential and ion activities of the epithelial cells of the rabbit ileum in vivo recorded by microelectrodes. Philos Trans R Soc Lond [Biol] 71:277–281

    Google Scholar 

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  1. M. Lucas
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  1. Department of Pharmacology, University of Missouri-Columbia School of Medicine, Columbia, MO, 65212, USA

    Tihamér Z. Csáky M.D. (Professor of Pharmacology) (Professor of Pharmacology)

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Lucas, M. (1984). The Surface pH of the Intestinal Mucosa and its Significance in the Permeability of Organic Anions. In: Csáky, T.Z. (eds) Pharmacology of Intestinal Permeation II. Handbook of Experimental Pharmacology, vol 70 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69508-7_3

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