Opioids II pp 163-190 | Cite as

Gastrointestinal Effects of Opioids

  • W. Kromer
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 2)


Although opioid alkaloids have been used as antidiarrheals for centuries, only during the last decade has it been recognized that endogenous opioid pep tides produce dual effects on gastrointestinal motility and intestinal chloride and gastric acid secretion. μ-, κ-, and δ-opioid receptors are involved and mediate opioid effects on neurons and smooth muscle cells by at least two different cellular mechanisms. The gastrointestinal opioid system physiologically interacts with several gastrointestinal neurotransmitters and serves as a neuromodulatory system. This chapter will discuss the current knowledge on gastrointestinal opioid effects, from the esophagus to the anal sphincter.


Opioid Receptor Vasoactive Intestinal Polypeptide Myenteric Plexus Kappa Opioid Receptor Chloride Secretion 
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  1. Abbott WO, Pendergrass EP (1936) Intubation studies of the human small intestine. V. The motor effects of single clinical doses of morphine sulphate in normal subjects. AJR 35:289–299Google Scholar
  2. Ahrens FA, Zhu BL (1982) Effects of epinephrine, clonidine, L-phenylephrine, and morphine on intestinal secretion mediated byEscherichia coli heat-stable enterotoxin in pig jejunum. Can J Physiol Pharmacol 60: 1680–1685PubMedCrossRefGoogle Scholar
  3. Ainsworth MA, Kjeldsen J, Schaffalitzky De, Muckadell OB (1990) Morphine inhibits secretion of bicarbonate from the human duodenal mucosa. Scand J Gastroenterol 25:1066–1075PubMedCrossRefGoogle Scholar
  4. Allescber HD, Ahmad S, Daniel EE, Dent J, Kostolanska F, Fox JET (1988) Inhibitory opioid receptors in canine pylorus. Am J Physiol 255:G352-G360Google Scholar
  5. Alvarez WC, Starkweather E (1918) The metabolic gradient underlying intestinal peristalsis. Am J Physiol 46:186–208Google Scholar
  6. Anderson W, Molina E, Rentz J, Hirschowitz BI (1982) Analysis of the 2-deoxY-Dglucose-induced vagal stimulation of gastric secretion and gastrin release in dogs using methionine-en kephalin, morphine and naloxone. J Pharmacol Exp Ther 222:617 -622PubMedGoogle Scholar
  7. Bardon T, Ruckebusch Y (1985) Comparative effects of opiate agonists on proximal and distal colonic motility in dogs. Eur J Pharmacol 110:329–334PubMedCrossRefGoogle Scholar
  8. Barrios M, Baeyens JM (1988) Differential effects of calcium channel blockers and stimulants on morphine withdrawal in vitro. Eur J Pharmacol 152:175–178PubMedCrossRefGoogle Scholar
  9. Basilisco G, Bozzani A, Camboni G, Recchia M, Quatrini M, Conte D, Penagini R, Bianchi PA (1985) Effect of loperamide and naloxone on mouth-to-caecum transit time evaluated by lactulose hydrogen breath test. Gut 26:700–703PubMedCrossRefGoogle Scholar
  10. Behar J, Biancani P (1984) Neural control of the sphincter of Oddi. Gastroenterology 86:134–141PubMedGoogle Scholar
  11. Bertiger G, Ouyang A, Reynolds JC, Cohen S (1988) Evidence for a direct and indirect action of leucine en kephalin at the feline ileocecal sphincter. Life Sci 42:1697–1703PubMedCrossRefGoogle Scholar
  12. Beubler E, Badhri P (1990) Comparison of the anti secretory effects of loperamide and loperamide oxide in the jejunum and the colon of rats in-vivo. J Ph arm Pharmacol 42:689–692CrossRefGoogle Scholar
  13. Beubler E, Lembeck F (1979) Inhibition of stimulated fluid secretion in the rat small and large intestine by opiate agonists. Naunyn Schmiedebergs Arch Pharmacol 306: 113–118PubMedCrossRefGoogle Scholar
  14. Beubler E, Lembeck F (1980) Inhibition by morphine of prostaglandin E1-stimulated secretion and cyclic adenosine 3′,5′ -mono phosphate formation in the rat jejunum in vivo. Br J Pharmacol 68:513–518PubMedGoogle Scholar
  15. Binder HJ, Laurenson JP, Dobbins JW (1984) Role of opiate receptors in regulation of enkephalin stimulation of active sodium and chloride absorption. Am J Physiol 247:G432-G436PubMedGoogle Scholar
  16. Bitar KN, Makhlouf GM (1985) Selective presence of opiate receptors on intestinal circular muscle cells. Life Sci 37:1545–1550PubMedCrossRefGoogle Scholar
  17. Bouvier M, Kirschner G, Gonella J (1986) Actions of morphine and enkephalins on the internal anal sphincter of the cat: relevance for the physiological role of opiates. J Auton Nerv Syst 16:219–232PubMedCrossRefGoogle Scholar
  18. Brown NJ, Coupar IM, David R, Rumsey E (1988) The effect of acute and chronic administration of morphine and morphine withdrawal on intestinal transit time in the rat. J Ph arm Pharmacol 40:844–848CrossRefGoogle Scholar
  19. Bueno L, Fioramonti J, Honde C, Fargeas MJ, Primi MP (1985) Central and peripheral control of gastrointestinal and colonic motility by endogenous opiates in conscious dogs. Gastroenterology 88:549–556PubMedGoogle Scholar
  20. Burks TF (1978) Central sites of action of gastrointestinal drugs. Gastroenterology 74:322–324PubMedGoogle Scholar
  21. Burks TF, Long JP (1967) Release of intestinal 5-hydroxytryptamine by morphine and related agents. J Pharmacol Exp Ther 156:267–276PubMedGoogle Scholar
  22. Burleigh DE (1988) Opioid and non-opioid actions of loperamide on cholinergic nerve function in human isolated colon. Eur J Pharmacol 152:39–46PubMedCrossRefGoogle Scholar
  23. Cherubini E, North RA (1985) μ and κ opioids inhibit transmitter release by different mechanisms. Proc Natl Acad Sci USA 82:1860–1863CrossRefGoogle Scholar
  24. Cherubini E, Morita K, North RA (1984) Morphine augments calcium-dependent potassium conductance in guinea-pig myenteric neurones. Br J Pharmacol 81:617–622PubMedGoogle Scholar
  25. Childers SR (1991) Opioid receptor-coupled second messenger systems. Life Sci 48:1991–2003PubMedCrossRefGoogle Scholar
  26. Clark SJ, Smith TW (1981) Peristalsis abolishes the release of methionine-enkephalin from guinea-pig ileum in vitro. Eur J Pharmacol 70:421–424PubMedCrossRefGoogle Scholar
  27. Collier HOJ, Plant NT, Tucker JF (1983) Pertussis vaccine inhibits the chronic but not acute action of normorphine on the myenteric plexus of guinea-pig ileum. Eur J Pharmacol 91:325–326PubMedCrossRefGoogle Scholar
  28. Costa M, Furness JB (1976) The peristaltic reflex: an analysis of the nerve pathways and their pharmacology. Naunyn Schmiedebergs Arch Pharmacol 294:47–60PubMedCrossRefGoogle Scholar
  29. Costa M, Furness JB, Cuello AC (1985) Separate populations of opioid containing neurons in the guinea-pig intestine. Neuropeptides 5:445–448PubMedCrossRefGoogle Scholar
  30. Culpepper-Morgan J, Kreek MJ, Holt PR, LaRoche D, Zhang J, O’Bryan L (1988) Orally administered kappa as well as mu opiate agonists delay gastrointestinal transit time in the guinea pig. Life Sci 42:2073–2077PubMedCrossRefGoogle Scholar
  31. Daniel EE, Fox JET, Allescher HD, Ahmad S, Kostolanska F (1987) Peripheral actions of opiates in canine gastrointestinal tract: actions on nerves and muscles. Gastroenterol Clin Bioi II:35B-43BGoogle Scholar
  32. Del Tacca M, Bernardini MC, Corsano E, Martinotti E, Rozé C (1989) Evidence for both inhibitory and excitatory effects of morphine on gastric secretion in the rat. Arch int Pharmacodyn Ther 297:178–189PubMedGoogle Scholar
  33. Dinari G, Ashkenazi S, Marcus H, Rosenbach Y, Zahavi I (1989) The effect of opiates on the intestinal immune response to cholera toxin in mice. Digestion 44:14–19PubMedCrossRefGoogle Scholar
  34. Dooley CP, Saad C, Valenzuela JE (1988) Studies of the role of opioids in control of human pancreatic secretion. Dig Dis Sci 33:598–604PubMedCrossRefGoogle Scholar
  35. Dowlatshahi K, Evander A, Walther B, Skinner DB (1985) Influence of morphine on the distal oesophagus and the lower oesophageal sphincter - a manometric study. Gut 26:802–806PubMedCrossRefGoogle Scholar
  36. Edin R, Lundberg J, Dahlstrom A, Hokfelt T, Terenius L, Ahlman H (1980) The peptidergic neural control of the feline pylorus. Chir Forum Exp Klin Forsch 233–237Google Scholar
  37. Erwin DN, Nonchoji T, Wood JD (1978) Effects of morphine on electrical activity of single myenteric neurons in cat small bowel. Eur J Pharmacol 47:401–405PubMedCrossRefGoogle Scholar
  38. Esplugues JV, Whittle BJR (1990) Morphine potentiation of ethanol-induced gastric mucosal damage in the rat. Gastroenterology 98:82–89PubMedGoogle Scholar
  39. Feldman M, Walsh JH, Taylor IL (1980) Effect of naloxone and morphine on gastric acid secretion and on serum gastrin and pancreatic polypeptide concentrations in humans. Gastroenterology 79:294–298PubMedGoogle Scholar
  40. Field M (1991) Intestinal ion transport mechanisms. In: Field M (ed) Diarrheal diseases, Elsevier, New York, pp 3–21Google Scholar
  41. Fioramonti J, Fargeas MJ, Buéno L (1984) Comparative effects of morphine and cyclazocine on gastrointestinal motility in conscious dogs. Arch Int Pharmacodyn Ther 270: 141–150PubMedGoogle Scholar
  42. Fischer EG, Falke NE (1984) β-Endorphin modulates immune functions. Psychother Psychosom 42:195–204PubMedCrossRefGoogle Scholar
  43. Flemström G, Jedstedt G, Nylander O (1986) β-Endorphin and enkephalins stimulate duodenal mucosal alkaline secretion in the rat in vivo. Gastroenterology 90:368–372PubMedGoogle Scholar
  44. Frantzides CT, Condon RE, Schulte WJ, Cowles V (1990) Effects of morphine on colonic myoelectric and motor activity in subhuman primates. Am J Physiol 258:G247–G252PubMedGoogle Scholar
  45. Gaginella TS, Wu ZC (1983) [D–Ala2, D–Met5NH2]–enkephalin inhibits acetylcholine release from the submucosal plexus of rat colon. J Pharm Pharmacol 35:823–825PubMedCrossRefGoogle Scholar
  46. Garzón J, Höllt V, Herz A (1987) Cholecystokinin octapeptide activates an opioid mechanism in the guinea-pig ileum: a possible role for substance P. Eur J Pharmacol 136:361–370PubMedCrossRefGoogle Scholar
  47. Gintzler AR, Xu H (1991) Different G proteins mediate the opioid inhibition or enhancement of evoked [5-methionine]enkephalin release. Proc NatI Acad Sci USA 88:4741–4745CrossRefGoogle Scholar
  48. Glavin GB, Pinsky C, Hall AM (1990) Effects of metkephamid (L Y127623), a selective delta opioid receptor agonist, on gastric function. Life Sci 46:1075–1079PubMedCrossRefGoogle Scholar
  49. Gmerek DE, Cowan A, Woods JH (1986) Independent central and peripheral mediation of morphine-induced inhibition of gastrointestinal transit in rats. J Pharmacol Exp Ther 236:8–13PubMedGoogle Scholar
  50. Grider JR, Makhlouf GM (1987) Role of opioid neurons in the regulation of intestinal peristalsis. Am J Physiol 253:G226-G231PubMedGoogle Scholar
  51. Grider JR, Makhlouf GM (1991) Identification of opioid receptors on gastric muscle cells by selective receptor protection. Am J Physiol 260:G103-G107PubMedGoogle Scholar
  52. Gué M, Fioramonti J, Honde C, Pascaud X, Junien JL, Bueno L (1988) Opposite effects of K-opioid agonists on gastric emptying of liquids and solids in dogs. Gastroenterology 95 :927 - 931PubMedGoogle Scholar
  53. Gué M, Junien JL, Bueno L (1989) Central and peripheral opioid modulation of gastric relaxation induced by feeding in dogs. J Pharmacol Exp Ther 250:1006–1010PubMedGoogle Scholar
  54. Gyires K (1990) Morphine inhibits the ethanol-induced gastric damage in rats. Arch Int Pharmacodyn Ther 306: 170–181PubMedGoogle Scholar
  55. Hall A W, Moossa AR, Clark J, Cooley GR, Skinner DB (1975) The effects of premedication drugs on the lower esophageal high pressure zone and reflux status of rhesus monkeys and man. Gut 16:347–352PubMedCrossRefGoogle Scholar
  56. Helm JF, Venu RP, Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Arndorfer RC (1988) Effects of morphine on the human sphincter of Oddi. Gut 29:1402–1407PubMedCrossRefGoogle Scholar
  57. Hescheler J, Rosenthal W, Trautwein W, Schultz G (1987) The GTP-binding protein, Go, regulates neuronal calcium channels. Nature 325:445–447PubMedCrossRefGoogle Scholar
  58. Hey VMF, Ostick DG, Mazumder JK, Lord WD (1981) Pethidine, metoclopramide, and the gastro-oesophageal sphincter. Anaesthesia 36: 173–176PubMedCrossRefGoogle Scholar
  59. Hirst GDS, McKirdy HC (1974) A nervous mechanism for descending inhibition in guinea-pig small intestine. J Physiol (Lon) 238:129–143Google Scholar
  60. Ho MM, Ogle CW, Dai S (1986) Effects of morphine, hypoxaemia and hypercapnia on the rat stomach. Eur J Pharmacol 126:103–109PubMedCrossRefGoogle Scholar
  61. Hodgkiss JP, Lees GM (1986) Transmission in enteric ganglia. In: Karczmar AG, Koketsu K, Nishi S (eds) Autonomic and enteric ganglia. Transmission and its pharmacology. Plenum, New York, 369–405Google Scholar
  62. Howard JM, Belsheim MR, Sullivan SN (1982) Enkephalin inhibits relaxation of the lower oesophageal sphincter. Br Med J 285:1605–1606CrossRefGoogle Scholar
  63. Hughes S, Higgs NB, Turnberg LA (1984) Loperamide has antisecretory activity in the human jejunum in vivo. Gut 25:931–935PubMedCrossRefGoogle Scholar
  64. Illes P (1989) Modulation of transmitter and hormone release by multiple neuronal opioid receptors. Rev Physiol Biochem Pharmacol 112:139–233PubMedCrossRefGoogle Scholar
  65. Jiang QI, Sheldon RJ, Porreca F (1990) Opioid modulation of basal intestinal fluid transport in the mouse: actions at central, but not intestinal, sites. J Pharmacol Exp Ther 253:784–790PubMedGoogle Scholar
  66. Johnson EE (1981) Morphine: a dual effect at the canine choledochoduodenal junction. J Pharmacol Exp Ther 219:274–280PubMedGoogle Scholar
  67. Johnson SM, Costa M, Humphreys CMS (1988) Opioid mu and kappa receptors on axons of cholinergic excitatory motor neurons supplying the circular muscle of guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol 338:397–400PubMedCrossRefGoogle Scholar
  68. Kachur JF, Miller RJ, Field M (1980) Control of guinea pig intestinal electrolyte secretion by a δ-opiate receptor. Proc Natl Acad Sci USA 77:2753–2756PubMedCrossRefGoogle Scholar
  69. Kleiman-Wexler RL, Adair CG, Ephgrave KS (1989) Pharmacokinetics of naloxone: an insight into the locus of effect on stress-ulceration. J Pharmacol Exp Ther 251:435–438PubMedGoogle Scholar
  70. Konturek SJ, Pawlik W, Walus KM, Coy DH, Schally AV (1978a) Methionineenkephalin stimulates gastric secretion and gastric mucosal blood flow. Proc Soc Exp BioI Med 158:156–160Google Scholar
  71. Konturek SJ, Tasler J, Cieszkowski M, Jaworek J, Coy DH, Schally A V (1978b) Inhibition of pancreatic secretion by enkephalin and morphine in dogs. Gastroenterology 74:851–855PubMedGoogle Scholar
  72. Konturek SJ, Thor P, Król R, Dembinski A, Schally AV (1980) Influence of methionine-enkephalin and morphine on myoelectric activity of small bowel. Am J Physiol 238:G384-G389PubMedGoogle Scholar
  73. Konturek SJ, Jaworek J, Bielanski W, Cieszkowski M, Dobrzanska M, Coy DH (1982) Comparison of enkephalin and atropine in the inhibition of vagally stimulated gastric and pancreatic secretion and gastrin and pancreatic polypeptide release in dogs. Peptides 3:601–606PubMedCrossRefGoogle Scholar
  74. Koppanyi T, Murphy WS (1933) The effect of morphine on the anal sphincters. Science 78:14PubMedCrossRefGoogle Scholar
  75. Koslo RJ, Vaught JL, Cowan A, Gmerek DE, Porreca F (1985) Intrathecal morphine slows gastrointestinal transit in rats. Eur J Pharmacol 119:243–246PubMedCrossRefGoogle Scholar
  76. Kostritsky-Pereira A, Woussen-Colle MC, De Graef J (1984) Effect of metenkephalin on acid secretion from gastric fistulas and Heidenhain pouches in dogs stimulated by pentagastrin, pentagastrin plus bethanechol, or a meal. Int J Tissue React 6:167–173PubMedGoogle Scholar
  77. Krevsky B, Cowan A, Maurer AH, Butt W, Fisher RS (1991) Effects of selective opioid agonists on feline colonic transit. Life Sci 48: 1597 -1602PubMedCrossRefGoogle Scholar
  78. Kromer W (1988) Endogenous and exogenous opioids in the control of gastrointestinal motility and secretion. Pharmacol Rev 40: 121–162PubMedGoogle Scholar
  79. Kromer W (1989) The current status of opioid research on gastrointestinal motility. Life Sci 44:579–589PubMedCrossRefGoogle Scholar
  80. Kromer W (1990a) Endogenous opioids, the enteric nervous system and gut motility. Dig Dis 8:361–373.PubMedCrossRefGoogle Scholar
  81. Kromer W (1990b) Reflex peristalsis in the guinea pig isolated ileum is endogenously controlled by kappa opioid receptors. Naunyn Schmiedebergs Arch Pharmacol 341:450–454PubMedGoogle Scholar
  82. Kromer W (1991) Voltage-clamp experiments reveal receptor type-dependent modulation of chloride secretion in the guinea pig colonic mucosa by intestinal opioids. Naunyn Schmiedebergs Arch Pharmacol 344:360–367CrossRefGoogle Scholar
  83. Kromer W, Pretzlaff W (1979) In vitro evidence for the participation of intestinal opioids in the control of peristalsis in the guinea pig small intestine. Naunyn Schmiedebergs Arch Pharmacol 309: 153–157PubMedCrossRefGoogle Scholar
  84. Kromer W, Schmidt H (1982) Opioids modulate intestinal peristalsis at a site of action additional to that modulating acetylcholine release. J Pharmacol Exp Ther 223:271–274PubMedGoogle Scholar
  85. Kromer W, Woinoff R (1980) Peristalsis in the isolated guinea-pig ileum during opiate withdrawal. Naunyn Schmiedebergs Arch Pharmacol 314:191–193PubMedCrossRefGoogle Scholar
  86. Kromer W, Pretzlaff W, Scheiblhuber E (1980a) In vitro evidence for an involvement of intestinal endorphins in the control of peristalsis in the guinea pig ileum. Comparison to rabbit, rat, cat and dog small intestine. In: Way EL (ed) Endogenous and exogenous opiate agonists and antagonists. Pergamon, New York, pp 337–340Google Scholar
  87. Kromer W, Pretzlaff W, Woinoff R (1980b) Opioids modulate periodicity rather than efficacy of peristaltic waves in the guinea pig ileum in vitro. Life Sci 26:1857–1865PubMedCrossRefGoogle Scholar
  88. Kromer W, Scheiblhuber E, Illes P (1980c) Functional antagonism by calcium of an intrinsic opioid mechanism in the guinea-pig isolated ileum. Neuropharmacology 19:839–843PubMedCrossRefGoogle Scholar
  89. Kromer W, Höllt V, Schmidt H, Herz A (1981a) Release of immunoreactivedynorphin from the isolated guinea pig small intestine is reduced during peristaltic activity. Neurosci Lett 25:53–56PubMedCrossRefGoogle Scholar
  90. Kromer W, Pretzlaff W, Woinoff R (1981b) Regional distribution of an opioid mechanism in the guinea-pig isolated intestine. J Pharm Pharmacol 33:98–101PubMedCrossRefGoogle Scholar
  91. Kromer W, Steigemann N, Shearman GT (1982) Differential effects of SKF 10,047 (N-allyl-normetazocine) on peristalsis and longitudinal muscle contractions of the isolated guinea-pig ileum. Naunyn Schmiedebergs Arch Pharmacol 321:218–222PubMedCrossRefGoogle Scholar
  92. Kromer W, Skowronek B, Stark H, Netz S (1983) Modulation of acid secretion from enriched guinea pig parietal cells by opioid receptors. Pharmacology 27:298–304PubMedCrossRefGoogle Scholar
  93. Lemcke PK, Shook JE, Burks TF (1991) Spinally mediated opioid antidiarrheal effects. Eur J Pharmacol 193: 109–115PubMedCrossRefGoogle Scholar
  94. Loeschke K, Schmid T, Farack UM (1989) Inhibition by loperamide of mucus secretion in the rat colon in vivo. Eur J Pharmacol 170:41–46PubMedCrossRefGoogle Scholar
  95. Lux B, Schulz R (1983) Cholera toxin selectively affects the expression of opioid dependence in the tolerant myenteric plexus of the guinea-pig. Eur J Pharmacol 96:175–176PubMedCrossRefGoogle Scholar
  96. Lux B, Schulz R (1986) Effect of cholera toxin and pertussis toxin on opioid tolerance and dependence in the guinea-pig myenteric plexus. J Pharmacol Exp Ther 237:995–1000PubMedGoogle Scholar
  97. Maas CL (1982) Opiate antagonists stimulate rumina I motility of conscious goats. Eur J Pharmacol 77:71–74PubMedCrossRefGoogle Scholar
  98. Mailman D (1980) Effects of morphine on canine intestinal absorption and blood flow. Br J Pharmacol 68:617–624PubMedGoogle Scholar
  99. Majeed NH, Lason W, Przewlocka B, Przewlocki R (1985) Serotonergic regulation of the brain and gut beta-endorphin and dynorphin content in the rat. Pol J Pharmacol Pharm 37:909–918PubMedGoogle Scholar
  100. Makhlouf GM (1987) Isolated smooth muscle cells of the gut. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York, pp 555–569Google Scholar
  101. Mannaioni PF (1984) Clinical pharmacology of drug dependence. Ishiyaku Euro America, Rock Island, pp 1–78Google Scholar
  102. McCallum RW, Dodds J, Osborne HP, Biancani P (1980) Effect of en kephalin and other opiates on opossum lower esophageal sphincter. In: Christensen J (ed) Gastrointestinal motility. Raven, New York, pp 37–41Google Scholar
  103. McKay JS, Linaker BD, Turnberg LA (1981) Influence of opiates on ion transport across rabbit ileal mucosa. Gastroenterology 80:279–284PubMedGoogle Scholar
  104. Megens AAHP, Canters LLJ, Awouters FHL, Niemegeers CJE (1989) Is in vivo dissociation beween the anti propulsive and antidiarrheal properties of opioids in rats related to gut selectivity? Arch Int Pharmacodyn Ther 298:220–229PubMedGoogle Scholar
  105. Megens AAHP, Canters LLJ, Awouters FHL, Niemegeers CJE (1990) Normalization of small intestinal propulsion with loperamide-like antidiarrheals in rats. Eur J Pharmacol 17:357–364CrossRefGoogle Scholar
  106. Mihara S, North RA (1986) Opioids increase potassium conductance in submucous neurons of guinea-pig caecum by activating δ-receptors. Br J Pharmacol 88:315–322PubMedGoogle Scholar
  107. Mittal RK, Frank EB, Lange RC, McCallum RW (1986) Effects of morphine and naloxone on esophageal motility and gastric emptying in man. Dig Dis Sci 31:963–942Google Scholar
  108. Miyazaki H, Nambu K, Hashimoto M (1982) Loperamide in rat intestines: a unique disposition. Life Sci 30:2203–2206PubMedCrossRefGoogle Scholar
  109. Nakayama S, Taniyama K, Matsuyama S, Ohgushi N, Tsunekawa K, Tanaka C (1990) Regulatory role of enteric mu and kappa opioid receptors in the release of acetylcholine and norepinephrine from guinea pig ileum. J Pharmacol Exp Ther 254:792–798PubMedGoogle Scholar
  110. North RA, Katayama Y, Williams JT (1979) On the mechanism and site of action of enkephalin on single myenteric neurons. Brain Res 165:67–77PubMedCrossRefGoogle Scholar
  111. North RA, Williams JT, Surprenant A, Christie MJ (1987) μ and δ receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci USA 84:5487–5491PubMedCrossRefGoogle Scholar
  112. Okamoto T, Kurahashi K, Tsubomura T, Fujiwara M (1986) Effects of morphine on hexamethonium-sensitive and -resistant excitatory responses of stomach to stimulation of vagal trunk in cats. Life Sci 39:147–153PubMedCrossRefGoogle Scholar
  113. Okamoto T, Kurahashi K, Fujiwara M (1988) Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats. Br J Pharmacol 95:329–334PubMedGoogle Scholar
  114. Ooms LAA, Degryse AD, Janssen PAJ (1984) Mechanisms of action of loperamide. Scand J Gastroenterol19 Suppl 96:145–155Google Scholar
  115. Ouyang A, Clain CJ, Snape WJ, Cohen S (1982) Characterization of opiatemediated responses of the feline ileum and ileocecal sphincter. J Clin Invest 69:507–515PubMedCrossRefGoogle Scholar
  116. Pairet M, Ruckebusch Y (1984) Opioid receptor agonists in the rabbit colon: comparison of in vivo and in vitro studies. Life Sci 35: 1653–1658PubMedCrossRefGoogle Scholar
  117. Parolaro D, Patrini G, Massi P, Parenti M, Rubino T, Giagnoni G, Gori E (1990) Pertussis toxin modifies the effect of central morphine on rat intestinal motility. Eur J Pharmacol 177:75–80PubMedCrossRefGoogle Scholar
  118. Pascaud XB, Genton MG, Remond G, Vincent M (1980) Antral to colonic motility responses to intracerebroventricular administration of o-Ala2-enkephalinamide, β-endorphin, methionine enkephalin, and fentanyl in anesthetized rats. In: Christensen J (ed) Gastrointestinal motility. Raven, New York, pp 459–466Google Scholar
  119. Polak JM, Sullivan SN, Bloom SR, Facer P, Pearse AGE (1977) Enkephalin-like immunoreactivity in the human gastrointestinal tract. Lancet 7:972–974CrossRefGoogle Scholar
  120. Porreca F, Burks TF (1983) The spinal cord as a site of opioid effects on gastrointestinal transit in the mouse. J Pharmacol Exp Ther 227:22–27PubMedGoogle Scholar
  121. Porreca F, Mosberg HI, Hurst R, Hruby VJ, Burks TF (1984) Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse. J Pharmacol Exp Ther 230:341–348PubMedGoogle Scholar
  122. Quigley JP, Highstone WH, Ivy AC (1934) Action of morphine, papaverine, atropine, pilocarpine, pituitrin, pitocin, and pitressin on intestinal propulsive activity determined in the unanesthetized dog by the bolus method. J Pharmacol Exp Ther 51:308–320Google Scholar
  123. Quito FL, Brown DR (1989) Jejunal pro absorptive actions of selective opiate agonists administered via the cerebral ventricles. Neuropeptides 14:39–44PubMedCrossRefGoogle Scholar
  124. Quito FL, Brown DR (1991) Neurohormonal regulation of ion transport in the porcine distal jejunum. Enhancement of sodium and chloride absorption by submucosal opiate receptors. J Pharmacol Exp Ther 256:833–840PubMedGoogle Scholar
  125. Rachmilewitz D, Karmeli F, Chorev M, Selinger Z (1983) Effect of opiates on human colonic adenylate cyclase activity. Eur J Pharmacol 93:169–173PubMedCrossRefGoogle Scholar
  126. Ramabadran K, Bansinath M, Turndorf H, Puig MM (1988) Stereospecific inhibition of gastrointestinal transit by κ opioid agonists in mice. Eur J Pharmacol 155:329–331PubMedCrossRefGoogle Scholar
  127. Rattan S, Culver PJ (1987) Influence of loperamide on the internal anal sphincter in the opossum. Gastroenterology 93:121–128PubMedGoogle Scholar
  128. Rattan S, Goyal RK (1983) Identification and localization of opioid receptors in the opossum lower esophageal sphincter. J Pharmacol Exp Ther 224:391–397PubMedGoogle Scholar
  129. Rees WDW, Gibbons LC, Turnberg LA (1986) Influence of opiates on alkali secretion by amphibian gastric and duodenal mucosa in vitro. Gastroenterology 90:323–327PubMedGoogle Scholar
  130. Reynolds JC, Ouyang A, Cohen S (1984) Evidence for an opiate-mediated pyloric sphincter reflex. Am J Physiol 246:G130-G136PubMedGoogle Scholar
  131. Riegel F (1900) Ober den EinfluB des Morphiums auf die Magensaftsecretion. Z Klin Med 40:347–368Google Scholar
  132. Rivière PJM, Liberge M, Murillo-Lopez D, Bueno L (1989) Opposite central and peripheral control by endogenous opioids of intestinal motility in fed rats. Br J Pharmacol 98:236–242PubMedGoogle Scholar
  133. Rozé C, Dubrasquet M, Chariot J, Vaille C (1982) Methadone inhibition of vagally induced pancreatic and gastric secretions in rats: central and peripheral sites of action. Eur J Pharmacol 78:271–278PubMedCrossRefGoogle Scholar
  134. Ruckebusch Y, Bardon T, Pairet M (1984) Opioid control of the ruminant stomach motility: functional importance of μ, κ and δ receptors. Life Sci 35:1731–1738PubMedCrossRefGoogle Scholar
  135. Sarna SK, Lang IM (1985) Dose- and time-dependent biphasic response to morphine on intestinal migrating myoelectric complex. J Pharmacol Exp Ther 234:814–820PubMedGoogle Scholar
  136. Sarna SK, Otterson MF (1990) Small intestinal amyogenesia and dysmyogenesia induced by morphine and loperamide. Am J Physiol 258:G282-G289PubMedGoogle Scholar
  137. Schang JC, Hemond M, Hebert M, Pilote M (1986) How does morphine work on colonic motility? An electromyographic study in the human left and sigmoid colon. Life Sci 38:671–676PubMedCrossRefGoogle Scholar
  138. Schepp W, Schneider J, Schusdziarra V, Classen M (1986) Naturally occurring opioid peptides modulate H+ -production by isolated rat parietal cells. Peptides 7:885–890PubMedCrossRefGoogle Scholar
  139. Schiller LR, Santa Ana CA, Morawski SG, Fordtran JS (1984) Mechanism of the antidiarrheal effect of loperamide. Gastroenterology 86:1475–1480PubMedGoogle Scholar
  140. Schulz R (1988) Dependence and cross-dependence in the guinea-pig myenteric plexus. Naunyn Schmiedebergs Arch Pharmacol 337:644–648PubMedGoogle Scholar
  141. Schulz R, Wüster M, Herz A (1979) Centrally and peripherally mediated inhibition of intestinal motility by opioids. Naunyn Schmiedebergs Arch Pharmacol 308:255–260PubMedCrossRefGoogle Scholar
  142. Schusdziarra V, Specht J, Schick R, De La Fuente A, Holland A, Pfeiffer EF (1983) Effect of morphine, leu-en kephalin and β-casomorphins on basal somatostatin release in dogs. Horm Metab Res 15:407–408PubMedCrossRefGoogle Scholar
  143. Sekiya K, Funakoshi A, Nakano I, Nawata H, Kato K, Ibayashi H (1986) Effect of methionine-enkephalin analog (FK 33–824) on plasma motilin. Gastroenterol Jpn 21:344–348PubMedGoogle Scholar
  144. Sheldon RJ, Riviere PJ, Malarchik ME, Moseberg HI, Burks TF, Porreca F (1990) Opioid regulation of mucosal ion transport in the mouse isolated jejunum. J Pharmacol Exp Ther 253:144–151PubMedGoogle Scholar
  145. Shook JE, Pelton JT, Hruby VJ, Burks TF (1987) Peptide opioid antagonist separates peripheral and central opioid antitransit effects. J Pharmacol Exp Ther 243:492–500PubMedGoogle Scholar
  146. Shook JE, Lemcke PK, Gehring CA, Hruby VJ, Burks TF (1989) Antidiarrheal properties of supraspinal mu and delta and peripheral mu, delta and kappa opioid receptors: inhibition of diarrhea without constipation. J Pharmacol Exp Ther 249:83–90PubMedGoogle Scholar
  147. Skov Olsen P, Kirkegaard P, Petersen B, Christiansen J (1982) Effect of naloxone on met-enkephalin-induced gastric acid secretion and serum gastrin in man. Gu 23:63–65CrossRefGoogle Scholar
  148. Smirnow AI, Schirokij WF (1927) Über den Einfluβ des Morphiums auf die Magensekretion bei niichternen Hunden. Z Gesamte Exp Med 57:324–336CrossRefGoogle Scholar
  149. Soldani G, Del Tacca M, Mengozzi G, Bernardini C, Bartolini D (1985) Central and peripheral involvement of 11 receptors in gastric secretory effects of opioids in the dog. Eur J Pharmacol 117:295–301PubMedCrossRefGoogle Scholar
  150. Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124PubMedCrossRefGoogle Scholar
  151. Stewart JJ (1981) Interactions of reserpine and morphine on rat intestinal transit. J Pharmacol Exp Ther 216:521–525PubMedGoogle Scholar
  152. Stoll R, Ruppin H, Domschke W (1988) Calmodulin-mediated effects of loperamide on chloride transport by brush border membrane vesicles from human ileum. Gastroenterology 95:69–76PubMedGoogle Scholar
  153. Strombeck DR, Harrold D (1985) Effects of atropine, acepromazine, meperidine, and xylazine on gastroesophageal sphincter pressure in the dog. Am J Vet Res 46:963–965PubMedGoogle Scholar
  154. Surprenant A, Shen KZ, North RA, Tatsumi H (1990) Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. J Physiol 431:585–608PubMedGoogle Scholar
  155. Tavani A, Petrillo P, La Regina A, Sbacchi M (1990) Role of peripheral mu, delta and kappa opioid receptors in opioid-induced inhibition of gastrointestinal transit in rats. J Pharmacol Exp Ther 254:91–97PubMedGoogle Scholar
  156. Tazi-Saad K, Chariot J, Vatier J, Del Tacca M, Rozé C (1991) Antisecretory and anti-ulcer effects of morphine in rats after gastric mucosal aggression. Eur J Pharmacol 192:271–277PubMedCrossRefGoogle Scholar
  157. Telford GL, Caudill A, Condon RE, Szurszewski JH (1988) Ketocyclazocine, a κ-opioid receptor agonist, and control of intestinal myoelectric activity in dogs. Am J Physiol 255:G566-G570PubMedGoogle Scholar
  158. Teschemacher H, Schweigerer L (1985) Opioid peptides: do they have immunological significance? Trends Pharmacol Sci 6:368–370CrossRefGoogle Scholar
  159. Till M, Gáti T, Rabai K, Szombath D, Szekely JI (1988) Effect of [D-Met2, Pro5]enkephalinamide on gastric ulceration and transmucosal potential difference. Eur J Pharmacol 150:325–330PubMedCrossRefGoogle Scholar
  160. Tougas G, Bovell KT, Collins SM, Dent J, Hunt RH (1990) The effect of naloxone on lipid-induced pyloric motor response in humans. Gastroenterology 99:930–934PubMedGoogle Scholar
  161. Touzeau PL, Shea-Donohue T (1990) Kappa agonists inhibit gastric emptying but not acid secretion in rhesus monkeys. J Pharmacol Exp Ther 253:1010–1016PubMedGoogle Scholar
  162. Tverskoy M, Gelman S, Fowler K, Bradley EL (1985) Influence of fentanyl and morphine on intestinal circulation. Anesth Analg 64:577–584PubMedCrossRefGoogle Scholar
  163. Valeri P, Martinelli B, Morrone LA, Severini C (1990) Reproducible withdrawal contractions of isolated guinea-pig ileum after brief morphine exposure: effects of c10nidine and nifedipine. J Pharm Pharmacol 42:115–120PubMedCrossRefGoogle Scholar
  164. Vaught JL, Cowan A, Jacoby HJ (1985) μ and δ, but not κ, opioid agonists induce contractions of the canine small intestine in vivo. Eur J Parmacol 109:43–48CrossRefGoogle Scholar
  165. Vinayek R, Brown DR, Miller RJ (1983) Inhibition of the antisecretory effects of [D-Ala2, D-Leu5]enkephalin in the guinea-pig ileum by a selective delta-opioid antagonist. Eur J Pharmacol 94: 159–161PubMedCrossRefGoogle Scholar
  166. Wang FS, Tsou K (1989) Substance P and [leucine]enkephalin release in guinea pig ileum during naloxone-precipitated morphine withdrawal. J Parmacol Exp Ther 249:329–332Google Scholar
  167. Ward SJ, Takemori AE (1982) Relative involvement of receptor subtypes in opioidinduced inhibition of intestinal motility in mice. Life Sci 31:1267–1270PubMedCrossRefGoogle Scholar
  168. Weisbrodt NW (1987) Motility of the small intestine. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven, New York, pp 631–663Google Scholar
  169. Wienbeck M, Blasberg M (1986) Effects of an enkephalin analog on motility of the small and large intestine in the cat. Z Gastroenterol 24: 179–187PubMedGoogle Scholar
  170. Wood JD (1980) Intracellular study of effects of morphine on electrical activity of myenteric neurons in cat small intestine. Gastroenterology 79:1222–1230PubMedGoogle Scholar
  171. Wood JD (1987) Physiology of the enteric nervous system. In: Johnson LR (ed) Physiology of the gastrointestinal tract, 2nd edn. Raven, New York, pp 67–109Google Scholar
  172. Worobetz LJ, Baker RJ, McCallum JA, Wells G, Sullivan SN (1982) The effect of naloxone, morphine, and an en kephalin analogue on cholecystokinin octapeptide-stimulated gallbladder emptying. Am J Gastroenterol 77:509–511PubMedGoogle Scholar
  173. Wüster M, Herz A (1978) Opiate agonist action of antidiarrheal agents in vitro and in vivo - findings in support for selective action. Naunyn Schmiedebergs Arch Pharmacol 301:187–194PubMedCrossRefGoogle Scholar
  174. Wüster M, Schulz R, Herz A (1985) Opioid tolerance and dependence: re-evaluating the unitary hypothesis. Trends Pharmacol Sci 6:64–67CrossRefGoogle Scholar
  175. Yagasaki O, Sasaki N, Yanagiya I (1982) Evidence of ascending release of acetylcholine from the locally distended guinea pig ileum. Jpn J Pharmacol 32:938–940PubMedCrossRefGoogle Scholar
  176. Yahya MD, Watson RR (1987) Immunomodulation by morphine and marijuana. Life Sci 41:2503–2510PubMedCrossRefGoogle Scholar
  177. Zavecz JH, Jackson TE, Limp GL, Yellin TO (1982) Relationship between antidiarrheal activity and binding to calmodulin. Eur J Pharmacol 78:375–377PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1993

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  • W. Kromer

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