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The Effect of Chemicals on Hepatic Heme Biosynthesis

Differences in Response to Porphyrin-Inducing Chemicals Between Chick Embryo Liver Cells, the 17-Day-Old Chick Embryo and Other Species

  • Chapter
Heme and Hemoproteins

Abstract

The administration of Sedormid (2-isopropylpent-4-enoylurea) to rabbits resulted in an experimental porphyria (Schmid and Schwartz, 1952) and the liver which was shown to be the major site of the metabolic disturbance contained large amounts of uro-, copro-, and proto-porphyrin. Sedormid (Fig. 1 a) has a structure closely similar to the barbiturate group of drugs (Fig. 1 b). Investigation of the relationship between structure and porphyrin inducing activity revealed the following requirements for activity: an allyl group together with either a cyclic ureide (as in the barbiturates), a ureide (as in Sedormid), or an acid amide [as in allylisopropylacetamide (AIA, Fig. 1 c)].

This work was supported by a grant from the Medical Research Council, Canada.

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References

  • Abbritti, G., De Matteis, F.: Decreased levels of cytochrome P-450 and catalase in hepatic porphyria caused by substituted acetamides and barbiturates. Importance of the allyl group in the molecule of the active drugs. Chem. biol. Interact. 4, 281–286 (1971)

    Article  Google Scholar 

  • Atsmon, A.: Personal communication (1975)

    Google Scholar 

  • Atsmon, A., Blum, I.: Treatment of acute porphyria variegata with propranolol. Lancet 1970 I,196–197

    Article  Google Scholar 

  • Blum, I., Schoenfeld, N., Atsmon, A.: The effect of DL-propranolol on δ-aminolevulinic acid synthetase activity and urinary excretion of porphyrins in allylisopropylacetamide-induced experimental porphyria. Biochim. biophys. Acta (Amst.) 320, 242–248 (1973)

    CAS  Google Scholar 

  • Brodie, B.B., Cosmides, G.J., Rail, D.P.: Toxicology and the biomedical sciences. Science 148, 1547–1554 (1965)

    Article  PubMed  CAS  Google Scholar 

  • Cowger, M.L., Labbe, R.F.: Contraindications of biological oxidation inhibitors in the treatment of porphyria. Lancet 1965 I, 88–89

    Article  Google Scholar 

  • Creighton, J.M., Marks, G.S.: Drug-induced porphyrin biosynthesis—I. The effect of porphyria-inducing drugs on N-demethylase activity of chick embryo liver. Biochem. Pharmacol. 18, 2040–2045 (1969)

    Article  PubMed  CAS  Google Scholar 

  • Creighton, J.M., Marks, G.S.: Drug-induced porphyrin biosynthesis—VII. Species, sex, and developmental differences in the generation of experimental porphyria. Canad. J. Physiol. Pharmacol. 50, 485–489 (1972)

    Article  CAS  Google Scholar 

  • Dean, G.: A report on propanidid, an intravenous anaesthetic in Porphyria variegata. S. Afr. med. J. 43, 227–229 (1969)

    PubMed  CAS  Google Scholar 

  • Dean, G.: The Porphyrins. 2nd ed., p. 132. Philadelphia — Montreal: J.B. Lippincott Co. 1971

    Google Scholar 

  • De Matteis, F.: Drugs and porphyria, S. Afr. J. Lab. clin. Med. 17, 126–133 (1971)

    Google Scholar 

  • De Matteis, F.: Disturbances of liver porphyrin metabolism caused by drugs. Pharmacol. Rev. 19, 523–557 (1967)

    PubMed  Google Scholar 

  • De Matteis, F.: Drug interactions in experimental hepatic porphyria. A model for the exacerbation by drugs of human variegate porphyria. Enzyme 16, 266–275 (1973)

    PubMed  Google Scholar 

  • De Matteis, F., Abbritti, G., Gibbs, A.H.: Decreased liver activity of porphyrin-metal chelatase in hepatic porphyria caused by 3,5-diethoxycarbonyl-l,4-dihydrocollidine. Biochem. J. 134, 717–727 (1973)

    PubMed  Google Scholar 

  • Doss, M., Kaltepoth, B.: Porphyrin biosynthesis in liver cell cultures. S. Afr. J. Lab. clin. Med. 17, 73–75 (1971)

    Google Scholar 

  • Eales, L.: Acute porphyria: The precipitating and aggravating factors. S. Afr. J. Lab. clin. Med. 17, 120–125 (1971)

    Google Scholar 

  • Edwards, A.M., Elliott, W.H.: Induction of δ-aminolevulinic acid synthetase in isolated rat liver cell suspensions. Adenosine 3′:5′-monophosphate dependence of induction by drugs. J. biol. Chem. 249, 851–855 (1974)

    PubMed  CAS  Google Scholar 

  • Edwards, A.M., Elliott, W.H.: Induction of 8-aminolevulinic acid synthetase in isolated rat liver cells by steroids. J. biol. Chem. 250, 2750–2755 (1975)

    PubMed  CAS  Google Scholar 

  • Finkelstein, R.A.: Observations on mode of action of endotoxin in chick embryos. Proc. Soc. exp. Biol. (N.Y.) 115, 702–707 (1964)

    CAS  Google Scholar 

  • Fischer, P.W.F., Morgan, R.O., Krupa, V., Marks, G.S.: Drug-induced porphyrin biosynthesis—XV. Induction of porphyrin biosynthesis in chick embryo liver cells maintained in serum-free Waymouth medium. Biochem. Pharmacol. 25, 687–693 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Goldberg, A.: The effects of certain barbiturates on the porphyrin metabolism of rabbits. Biochem. J. 57, 55–61 (1954)

    PubMed  CAS  Google Scholar 

  • Goldberg, A., Rimington, C.: Experimentally produced porphyria in animals. Proc. roy. Soc. B 143, 257–280 (1955)

    Article  CAS  Google Scholar 

  • Granick, S.: A test for detection of porphyria-inducing drugs. J. Amer. med. Ass. 190, 475 (1964)

    Google Scholar 

  • Granick, S.: The induction in vitro of the synthesis of δ-aminolevulinic acid synthetase in chemical porphyria: A response to certain drugs, sex hormones and foreign chemicals. J. biol. Chem. 241, 1359–1375 (1966)

    PubMed  CAS  Google Scholar 

  • Granick, S., Kappas, A.: Steroid control of porphyrin and heme biosynthesis: A new biological function of steroid hormone metabolites. Proc. nat. Acad. Sci. (Wash.) 57, 1463–1467 (1967a)

    Article  CAS  Google Scholar 

  • Granick, S., Kappas, A.: Steroid induction of porphyrin synthesis in liver cell culture. I. Structural basis and possible physiological role in the control of heme formation. J. biol. Chem. 24, 4587–4593 (1967b)

    Google Scholar 

  • Granick, S., Sassa, S.: δ-Aminolevulinic acid synthetase and the control of heme and chlorophyll synthesis. In: Metabolic Regulation. Vogel H.J. (ed.), Vol. 5 of Metabolic Pathways, pp. 77–141. New York–London: Academic Press 1971

    Google Scholar 

  • Granick, S., Sinclair, P., Sassa, S., Grieninger, G.: Effects by heme, insulin, and serum albumin on heme and protein synthesis in chick embryo liver cells cultured in a chemically defined medium, and a spectrofluorometric assay for porphyrin composition. J. biol. Chem. 250, 9215–9225 (1975)

    PubMed  CAS  Google Scholar 

  • Gross, S.R., Hutton, J.J.: Induction of hepatic δ-aminolevulinic acid synthetase activity in strains of inbred mice. J. biol. Chem. 246, 606–614 (1971)

    PubMed  CAS  Google Scholar 

  • Hansch, C.: Quantitative relationships between lipophilic character and drug metabolism. Drug Metab. Rev. 1, 1–14 (1972)

    Article  Google Scholar 

  • Hansch, C., Clayton, J.M.: Lipophilic character and biological activity of drugs II: The parabolic case. J. pharm. Sci. 62, 1–21 (1973)

    Article  PubMed  CAS  Google Scholar 

  • Hansch, C., Dunn, W.J.: Linear relationship between lipophilic character and biological activity of drugs. J. pharm. Sci. 61, 1–19 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Hansch, C., Steward, A.R., Anderson, S.M., Bentley, D.: The parabolic dependence of drug action upon lipophilic character as revealed by a study of hypnotics. J. med. Chem. 11, 1–11 (1968)

    Article  PubMed  CAS  Google Scholar 

  • Hayashi, N., Kurashima, Y., Kikuchi, G.: Mechanism of allylisopropylacetamide-induced increase of δ-aminolevulinate synthetase in liver mitochondria. V. Mechanism of regulation by hemin of the level of δ-aminolevulinate synthetase in rat liver mitochondria. Arch. Biochem. Biophys. 148, 10–21 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Heymann, E., Krisch, K., Buch, H., Buzello, W.: Inhibition of phenacetin- and acetanilide-induced methemoglobinemia in the rat by the carboxylesterase inhibitor bis-[p-nitrophenyl] phosphate. Biochem. Pharmacol. 18, 801 -811 (1969)

    Article  PubMed  CAS  Google Scholar 

  • Hirsch, G.H., Bubbar, G.L., Marks, G.S.: Studies of the relationship between chemical structure and porphyria-inducing activity—III. Biochem. Pharmacol. 16, 1455–1462 (1967)

    Article  PubMed  CAS  Google Scholar 

  • Hirsch, G.H., Gillis, J.D., Marks, G.S.: Studies of the relationship between chemical structure and porphyria-inducing activity—II. Biochem. Pharmacol. 15, 1006–1008 (1966)

    Article  CAS  Google Scholar 

  • Hutton, J.J., Gross, S.R.: Chemical induction of hepatic porphyria in inbred strains of mice. Arch. Biochem. Biophys. 141, 284–292 (1970)

    Article  PubMed  CAS  Google Scholar 

  • Jacob, F., Monod, J.: Genetic regulatory mechanisms in the synthesis of proteins. J. molec. Biol. 3, 318–356 (1961)

    Article  PubMed  CAS  Google Scholar 

  • Kappas, A., Granick, S.: Steroid induction of porphyrin synthesis in liver cell culture II. The effects of heme, uridine diphosphate glucuronic acid, and inhibitors of nucleic acid and protein synthesis on the induction process. J. biol. Chem. 243, 346–351 (1968)

    PubMed  CAS  Google Scholar 

  • Kappas, A., Song, C.S., Levere, R.D., Sachson, R.A., Granick, S.: The induction of δ-aminolevulinic acid synthetase in vivo in chick embryo liver by natural steroids. Proc. nat. Acad. Sci. (Wash.) 61, 509–513 (1968)

    Article  CAS  Google Scholar 

  • Koskelo, P., Eisalo, A., Toivonen, I.: Urinary excretion of porphyrin precursors and coproporphyrin in healthy females on oral contraceptives. Brit. med. J. 1966 I, 652–654

    Article  Google Scholar 

  • Krisch, K.: Carboxylic ester hydrolases. In: The Enzymes 3rd ed., Vol. 5, edit, by P.D. Boyer, pp. 43–69. New York — London: Academic Press 1972

    Google Scholar 

  • Krupa, V., Blattei, R.A., Marks, G.S.: Drug-induced porphyrin biosynthesis—IX. Levels of 14C-allylisopropylacetamide, 14C-propylisopropylacetamide and metabolite(s) in the livers of chick embryos and mice. Enzyme 16, 276–285 (1973)

    PubMed  CAS  Google Scholar 

  • Krupa, V., Creighton, J.C., Freeman, M., Marks, G.S.: Drug-induced porphyrin biosynthesis—XII. Levels of cytochrome P-450 in chick embryo liver following administration of allylisopropylacetamide and propylisopropylacetamide. Canad. J. Physiol. Pharmacol. 52, 891–895 (1974)

    Article  CAS  Google Scholar 

  • Leo, A., Hansch, C., Elkins, D.: Partition coefficients and their uses. Chem. Rev. 71, 525–616 (1971)

    Article  CAS  Google Scholar 

  • Marks, G.S.: Unpublished observations (1975)

    Google Scholar 

  • Marks, G.S., Hunter, E.G., Terner, U.K., Schneck, D.: Studies of the relationship between chemical structure and porphyria-inducing activity. Biochem. Pharmacol. 14, 1077–1084 (1965)

    Article  PubMed  CAS  Google Scholar 

  • Marks, G.S., Krupa, V., Murphy, F., Taub, H., Blattei, R.A.: Mechanisms of drug-induced porphyrin biosynthesis. Ann. N.Y. Acad. Sci. 244, 472–480 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Marks, G.S., Krupa, V., Roomi, M.W.: Drug-induced porphyrin biosynthesis—VIII. Investigation of the importance of an allyl group for activity in substituted acetamides. Canad. J. Physiol. Pharmacol. 51, 863–868 (1973)

    Article  CAS  Google Scholar 

  • Meyer, U.A., Strand, L.J., Doss, M., Rees, A.C., Marver, H.S.: Intermittent acute porphyria-demonstration of a genetic defect in porphobilinogen metabolism. New Engl. J. Med. 286, 1277–1282 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Moore, M.R., Battistini, V., Beattie, A.D., Goldberg, A.: The effects of certain barbiturates on the hepatic porphyrin metabolism of rats. Biochem. Pharmacol. 19, 751–757 (1970)

    Article  PubMed  CAS  Google Scholar 

  • Morgan, R.O., Fischer, P.W.F., Marks, G.S.: Unpublished observations (1976)

    Google Scholar 

  • Morgan, R.O., Fischer, P.W.F., Stephens, J.K., Marks, G.S.: Thyroid hormone enhancement of drug-induced porphyrin biosynthesis in chick embryo liver cells maintained in serum-free Waymouth medium. Biochem. Pharmacol. 25, 2609–2612 (1976)

    PubMed  CAS  Google Scholar 

  • Murphy, F.R., Krupa, V., Marks, G.S.: Drug-induced porphyrin biosynthesis—XIII. Role of lipophilicity in determining porphyrin-inducing activity of aliphatic amides after blockade of their hydrolysis by bis-[p-nitrophenyl] phosphate. Biochem. Pharmacol. 24, 883–889 (1975)

    Article  PubMed  CAS  Google Scholar 

  • Murphy, F.R., Krupa, V., Marks, G.S.: Drug-induced porphyrin biosynthesis—XIV. Role of lipophilicity in determining porphyrin-inducing activity of esters and amides following blockade of their hydrolysis by bis-[p-nitrophenyl) phosphate. Biochem. Pharmacol. 25, 1351–1354 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Murthy, V.V., Woods, J.S.: Solubilization and partial purification of mitochondrial δ-aminolevulinate synthase from fetal rat liver. Biochim. biophys. Acta (Amst.) 350, 240–246 (1974)

    CAS  Google Scholar 

  • Nebert, D.W., Gelboin, H.V.: The role of ribonucleic acid and protein synthesis in microsomal aryl hydrocarbon hydroxylase induction in cell cultures: The independence of transcription and translation. J. biol. Chem. 245, 160–168 (1970)

    PubMed  CAS  Google Scholar 

  • Ohashi, A., Kikuchi, G.: Mechanism of allylisopropylacetamide-induced increase of δ-aminolevulinate synthetase in liver mitochondria. VI. Multiple molecular forms of δ-aminolevulinate synthetase in the cytosol and mitochondria of induced cock liver. Arch. Biochem. Biophys. 153, 34–46 (1972)

    Article  CAS  Google Scholar 

  • Peterkofsky, B., Tomkins, G.M.: Evidence for the steroid-induced accumulation of tyrosine aminotransferase messenger RNA in the absence of protein synthesis. Proc. nat. Acad. Sci. (Wash.) 60, 222–228 (1968)

    Article  CAS  Google Scholar 

  • Poland, A., Glover, E.: 2,3,7,8-Tetrachlorodibenzo-p-dioxin: A potent inducer of δ-aminolevulinic acid synthetase. Science 179, 476–477 (1973a)

    Article  PubMed  CAS  Google Scholar 

  • Poland, A., Glover, E.: Chlorinated dibenzo-p-dioxins: Potent inducers of δ-aminolevulinic acid synthetase and aryl hydrocarbon hydroxylase. II. A study of the structure-activity relationship. Molec. Pharmacol. 9, 736–747 (1973b)

    CAS  Google Scholar 

  • Racz, W.J., Marks, G.S.: Drug-induced porphyrin biosynthesis—II. Simple procedure for screening drugs for porphyria-inducing activity. Biochem. Pharmacol. 18, 2009–2018 (1969)

    Article  PubMed  CAS  Google Scholar 

  • Racz, W.J., Marks, G.S.: Drug-induced porphyrin biosynthesis—IV. Investigation of the differences in response of isolated liver cells and the liver of the intact chick embryo to porphyria-inducing drugs. Biochem. Pharmacol. 21, 143–151 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Racz, W.J. Moffat, J.A.: Drug metabolism in cell culture—I. Importance of steric factors for activity in porphyrin-inducing drugs. Biochem. Pharmacol. 23, 215–221 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Rifkind, A.B., Gillette, P.N. Song, C.S., Kappas, A.: Induction of hepatic δ-aminolevulinic acid synthetase by oral contraceptive steroids. J. clin. Endocr. 30, 330–335 (1970)

    Article  PubMed  CAS  Google Scholar 

  • Rifkind, A.B., Gillette, P.N., Song, C.S., Kappas, A.: Drug stimulation of δ-aminolevulinic acid synthetase and cytochrome P-450 in vivo in chick embryo liver. J. Pharmacol, exp. Ther. 185, 214–225 (1973)

    CAS  Google Scholar 

  • Sassa, S., Granick, S.: Induction of δ-aminolevulinic acid synthetase in chick embryo liver cells in culture. Proc. nat. Acad. Sci. (Wash.) 67, 517–522 (1970)

    Article  CAS  Google Scholar 

  • Schlesinger, F.G., Gastel (van), C.: Possible aggravation of abdominal symptoms by tolbutamide in a patient with diabetes and hepatic porphyria. Acta med. scand. 169, 433–435 (1961)

    Article  PubMed  CAS  Google Scholar 

  • Schmid, R., Schwartz, S.: Experimental porphyria III. Hepatic type produced by Sedormid. Proc. Soc. exp. Biol. (N.Y.) 81, 685–689 (1952)

    CAS  Google Scholar 

  • Schneck, D.W., Marks, G.S.: The inhibition of drug-induced porphyria by hemin. Pharmacologist 11, 285 (1969)

    Google Scholar 

  • Schneck, D.W., Racz, W.J., Hirsch, G.H., Bubbar, G.L., Marks, G.S.: Studies of the relationship between chemical structure and porphyria-inducing activity—IV. Investigations in a cell culture system. Biochem. Pharmacol. 17, 1385–1399 (1968)

    Article  PubMed  CAS  Google Scholar 

  • Sinclair, P.R., Granick, S.: Uroporphyrin formation induced by chlorinated hydrocarbons (lindane, polychlorinated biphenyls, tetrachlorodibenzo-p-dioxin). Requirements for endogenous iron, protein synthesis and drug-metabolizing activity. Biochem. biophys. Res. Commun. 61, 124–133 (1974)

    Article  PubMed  CAS  Google Scholar 

  • Song, C.S., Bonkowsky, H.L., Tschudy, D.P.: Salicylamide metabolism in acute intermittent porphyria. Clin. Pharmacol. Ther. 15, 431–435 (1974)

    PubMed  CAS  Google Scholar 

  • Song, C.S., Singer, J.W., Levere, R.D., Harris, D.F., Kappas, A.: Developmental and gestational influences on drug induction of 5-aminolevulinic acid (ALA) synthetase in rat liver. J. Lab. clin. Med. 72, 1019–1020 (1968)

    Google Scholar 

  • Stich, W., Decker, P.: Studies on the mechanism of porphyrin biosynthesis with the aid of inhibitors. In: Ciba Foundation Symposium on Porphyrin Biosynthesis and Metabolism. Wolstenholme, G.E.W. Miller and Miller, E.C.P. (eds.), pp. 254–260. London: J. and A. Churchill 1955

    Google Scholar 

  • Strand, L.J., Manning, J., Marver, H.S.: The induction of δ-aminolevulinic acid synthetase in cultured liver cells. The effects of end product and inhibitors of heme synthesis. J. biol. Chem. 247, 2820–2827 (1972)

    PubMed  CAS  Google Scholar 

  • Strik, J.J.T.W.A.: Chemical porphyria in Japanese quail (Coturnix c. Japonka). Enzyme 16, 211–223 (1973)

    PubMed  CAS  Google Scholar 

  • Strik, J.J.T.W.A., Wit, J.G.: Hepatic porphyria in birds and mammals. TNO-nieuws 27, 604–610 (1972)

    CAS  Google Scholar 

  • Strittmatter, C.F., Umberger, F.T.: Oxidative enzyme components of avian liver microsomes. Changes during embryonic development and the effects of phenobarbital administration. Biochim. biophys. Acta (Amst.) 180, 18–27 (1969)

    Article  CAS  Google Scholar 

  • Talman, E.L., Labbe, R.F., Aldrich, R.A.: Porphyrin metabolism. IV. Molecular structure of acetamide derivatives affecting porphyrin metabolism. Arch. Biochem. Biophys. 66, 289–300 (1957)

    Article  CAS  Google Scholar 

  • Taub, H.: Drug-induced porphyrin biosynthesis. Effects of lipophilicity and hepatic metabolism on the porphyria-inducing activity of sedative-hypnotic drugs. M. Sc. Thesis, Queen’s University, Kingston, Canada (1973)

    Google Scholar 

  • Taub, H., Krupa, V., Marks, G.S.: Drug-induced porphyrin biosynthesis—XI. Effect of SKF 525-A on the activity of porphyrin-inducing drugs in chick embryos, chickens and rats. Biochem. Pharmacol. 25, 511–516 (1976)

    Article  PubMed  CAS  Google Scholar 

  • Taub, H., Marks, G.S.: Drug-induced porphyrin biosynthesis—X. Potentiation of propanidid-induced elevation of δ-aminolevulinic acid synthetase and porphyrins in chick embryo liver by the carboxylesterase inhibitor bis-[p-nitrophenyl] phosphate. Canad. J. Physiol. Pharmacol. 51, 700–704 (1973)

    Article  CAS  Google Scholar 

  • Tomita, Y., Ohashi, A., Kikuchi, G.: Induction of δ-aminolevulinate synthetase in organ culture of chick embryo liver by allylisopropylacetamide and 3,5-dicarbethoxy-l,4-dihydro-collidine. J. Biochem. 75, 1007–1015 (1974)

    CAS  Google Scholar 

  • Tyrrell, D.L.J., Marks, G.S.: Drug-induced porphyrin biosynthesis—V. Effect of protohemin on the transcriptional and post-transcriptional phases of 8-aminolevulinic acid synthetase induction. Biochem. Pharmacol. 21, 2077–2093 (1972)

    Article  PubMed  CAS  Google Scholar 

  • Vos, J.G., Botterweg, P.F., Strik, J.J.T.W.A., Koeman, J.H.: Experimental studies with HCB in birds. TNO-news, 27, 599–603 (1972)

    CAS  Google Scholar 

  • Watson, C.J.: Pursuit of the purple. J. Amer. med. Ass. 197, 1074–1080 (1966)

    Article  CAS  Google Scholar 

  • Watson, C.J.: Private communication (1974)

    Google Scholar 

  • Woods, J.S., Dixon, R.L.: Neonatal differences in the induction of hepatic aminolevulinic acid synthetase. Biochem. Pharmacol. 19, 1951–1954 (1970a)

    Article  PubMed  CAS  Google Scholar 

  • Woods, J.S., Dixon, R.L.: Perinatal differences in delta-aminolevulinic acid synthetase activity. Life Sci. 9, 711–719 (1970b)

    Article  CAS  Google Scholar 

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  1. Gerald S. Marks
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Marks, G.S. (1978). The Effect of Chemicals on Hepatic Heme Biosynthesis. In: De Matteis, F., Aldridge, W.N. (eds) Heme and Hemoproteins. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-66763-3_7

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