Skip to main content
SpringerLink
Log in

Reaction of drugs with microsomal liver hydroxylase: Its influence on drug action

  • Teil I Symposium
  • Published:
Naunyn-Schmiedebergs Archiv für Pharmakologie und experimentelle Pathologie Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Anders, M. W., and G. J. Mannering: Inhibition of drug metabolism. Mol. Pharmacol. 2, 319 (1966).

    Google Scholar 

  2. Ariens, E. J., J. M. van Rossum, and A. M. Simonis: Affinity, intrinsic activity and drug interactions. Pharmacol. Rev. 9, 218 (1967).

    Google Scholar 

  3. Axelrod, J.: Biochemical factors in the activation and inactivation of drugs. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 238, 24 (1960).

    Google Scholar 

  4. Brodie, B. B., J. R. Gillette, and B. N. La Du: Enzymatic metabolism of drugs and other foreign compounds. Ann. Rev. Biochem. 27, 427 (1958).

    Google Scholar 

  5. Butler, T. C.: The metabolic conversion of 5,5-diphenylhydantoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin. J. Pharmacol. exp. Ther. 119, 1 (1957).

    Google Scholar 

  6. Clark, A. J.: General Pharmacology. In: Heffters Handbuch der experimentellen Pharmakologie. Vol. IV. Berlin: Springer 1937.

    Google Scholar 

  7. Conney, A. H., C. Davison, R. Gastel, and J. J. Burns: Adaptive increase in drug metabolizing enzymes induced by phenobarbital and other drugs. J. Pharmacol. exp. Ther. 130, 1 (1960).

    Google Scholar 

  8. ——, and G. A. Miller: Evidence for induction of enzymes synthesis in the rat by 3-methylcholanthrene. Cancer Res. 16, 450 (1956).

    Google Scholar 

  9. Cooper, D. Y., S. Levin, S. Narasimkulu, O. Rosenthal, and R. W. Estabrook: Photochemical action spectrum of the terminal oxidase of mixed function oxidase systems. Science 147, 400 (1965).

    Google Scholar 

  10. Cucinell, S. A., A. H. Conney, M. Sansur, and J. J. Burns: Drug interaction in man. I. Lowering effect of phenobarbital on plasma levels of dishydroxycoumarin (Dicoumarol) and diphenylhydantoin (Dilantin). Clin. Pharmacol. Ther. 6, 420 (1965).

    Google Scholar 

  11. Estabrook, R. W., D. Y. Cooper, and O. Rosenthal: The light reversible monoxide inhibition of the steroid C 21-hydroxylase system of the adrenal cortex. Biochem. Z. 338, 741 (1963).

    Google Scholar 

  12. Fouts, J. R.: The metabolism of drugs by subfractions of hepatic microsomes-Biochem. biophys. Res. Commun. 6, 373 (1961).

    Google Scholar 

  13. ——, and L. A. Rogers: Morphological changes in the liver accompanying stimulation of microsomal drug metabolizing enzyme activity by phenobarbital, chlordane, benzpyrene or methylcholanthrene in rats. J. Pharmacol. exp. Ther. 147, 112 (1965).

    Google Scholar 

  14. Gaddum, J. H.: Theories of drug antagonism. Pharmacol. Rev. 9, 211 (1957).

    Google Scholar 

  15. Gillette, J. R.: Factors that affect the stimulation of the microsomal drug enzymes induced by foreign compounds. Sympos. Regulation of Enzyme Activity and Synthesis in normal and neoplastic liver. Bloomington, Indiana: Indiana University Press 1962.

    Google Scholar 

  16. Greim, H., u. H. Remmer: Die Wirkung von DDT und Phenobarbital auf hydroxylierende mikrosomale Cytochrome. Naunyns-Schmiedebergs Arch. Pharmak. exp. Path. 255, 16 (1966).

    Google Scholar 

  17. Hayaishi, O.: Proc. Plenary Session, 6th Internat. Congr. of Biochem., New York, Juli 1964, p. 31.

  18. Heubner, W.: Methämoglobin-bildende Gifte. Ergebn. Physiol. 43, 9 (1940).

    Google Scholar 

  19. Hildebrandt, A., H. Greim, R. W. Estabrook, and H. Remmer: Unpublished.

  20. Kampffmeyer, H., u. M. Kiese: Einige Eigenschaften der Anilin-hydroxylierenden Enzyme in Mikrosomen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 244, 375 (1963).

    Google Scholar 

  21. Kato, R.: Induced increase of meprobamate metabolism in rats treated with phenobarbital or phenaglycodol. Med. exp. (Basel) 3, 95 (1960).

    Google Scholar 

  22. Kinoshita, T., and S. Horie: Studies on P450. III. On the absorption spectrum of P450 in rabbit liver microsomes. J. Biochem. (Tokyo) 61, 26 (1967).

    Google Scholar 

  23. Klingenberg, M.: Pigments of rat liver microsomes. Arch. Biochem. 75, 376 (1958).

    Google Scholar 

  24. Kutt, H., M. Wolk, R. Scherman, and F. Mc Dowell: Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology (Minneap.) 14, 542 (1964).

    Google Scholar 

  25. Lange, G.: Verschiedene Induktion der mikrosomalen N- und p-Hydroxylierung von Anilin und N-Äthylanilin bei Kaninchen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 257, 230 (1967).

    Google Scholar 

  26. Mason, H. S.: Mechanism of oxygen metabolism. Advanc. Enzymol. 19, 79 (1957).

    Google Scholar 

  27. Michaelis, L., u. M. L. Menten: Die Kinetik der Invertinwirkung. Biochem. Z. 49, 333 (1913).

    Google Scholar 

  28. Morita, Y., and H. S. Mason: An electron spin resonance study of some hemoproteins. J. biol. Chem. 240, 6 (1965).

    Google Scholar 

  29. Omura, T., and R. Sato: The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. biol. Chem. 239, 7 (1964).

    Google Scholar 

  30. —— —— The carbon monoxide-binding pigment of liver microsomes. II. Solubilization, purification, and properties. J. biol. Chem. 239, 2379 (1964).

    Google Scholar 

  31. -- -- Personal communication.

  32. Orrenius, S., J. Ericson, and L. Ernster: Phenobarbital-induced synthesis of the microsomal drug-metabolizing enzyme system. J. Cell. Biol. 25, 627 (1965).

    Google Scholar 

  33. Paton, W. D. M.: A theory of drug action based on the rate of drug receptor comhination. Proc. roy. Soc. B 154, 21 (1961).

    Google Scholar 

  34. Quinn, G. P., J. Axelrod, and B. B. Brodie: Species, strain and sex differences in metabolism of hexobarbitone, amidopyrine, antipyrine and aniline. Biochem. Pharmacol. 1, 152 (1958).

    Google Scholar 

  35. Remmer, H.: Die Beschleunigung des Abbaues als Ursache der Gewöhnung an Barbiturate. Naturwissenschaften 46, 580 (1959).

    Google Scholar 

  36. —— Der beschleunigte Abbau von Pharmaka in den Lebermikrosomen unter dem Einfluß von Luminal. Naunyn-Schmiedebergs Arch. exp. Path. Arch. 235, 279 (1959).

    Google Scholar 

  37. -- Drug-Induced Formation of smooth endoplasmic reticulum and of drug metabolizing enzymes. Proc. Europ. Soc. Study of Drug Toxic., Vol. IV, Cambridge, 1964.

  38. -- I. Greiner, J. Hirschmann, and J. Renne: Unpublished.

  39. ——, and O. Rosenthal: Drug interaction with hepatic microsomal cytochrome. Molec. Pharmacol. 2, 187 (1966).

    Google Scholar 

  40. ——, u. M. Siegert: Beschleunigter Arzneimittelabbau durch Enzyminduktion beim Hunde nach Behandlung mit Phenobarbital. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 247, 522 (1964).

    Google Scholar 

  41. —— —— u. H.-J. Merker: Vermehrung arzneimittelabbauender Enzyme durch Tolbutamid. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 249, 71 (1964).

    Google Scholar 

  42. Schenkman, J. B., I. Frey, H. Remmer, and R. W. Estabrook: Sex differences in drug metabolism by rat liver microsomes. Molec. Pharmacol. (in press).

  43. ——, and R. W. Estabrook: Spectral studies of drug interaction with hepatic microsomal cytochrome. Molec. Pharmacol. 3, 113 (1967).

    Google Scholar 

  44. Strittmatter, P., and F. S. Velick: The isolation of microsomal cytochromes. J. biol. Chem. 221, 253 (1956).

    Google Scholar 

  45. Uehleke, H.: Stimulierung einiger mikrosomaler Fremdstoff-Oxydationen durch Phenobarbital, Methylcholanthren und Chlorphenothan. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. (in press).

  46. Wilson, I. B., F. Bergmann, and D. Nachmansohn: Acetylcholinesterase: V. Mechanism of the catalysis of acylation reactions. J. biol. Chem. 186, 781 (1950).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Toxikologie der Universität, Wilhelmstr. 56, 7400, Tübingen

    H. Remmer

Authors
  1. H. Remmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. W. Estabrook
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Schenkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Greim
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

The experiments described in this lecture were carried out in collaboration of the Institut für Toxikologie, Universität Tübingen with the Department of Biophysics and Physical Biochemistry, University of Pennsylvania in Philadelphia/USA.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Remmer, H., Estabrook, R.W., Schenkman, J. et al. Reaction of drugs with microsomal liver hydroxylase: Its influence on drug action. Naunyn-Schmiedebergs Arch. Pharmak. u. Exp. Path. 259, 98–116 (1968). https://doi.org/10.1007/BF00537741

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00537741

Keywords

Search

Navigation