Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 294, Issue 2, pp 199–206 | Cite as

Adrenal cortex adenylate cyclase

In vitro activity of ACTH fragments and analogues
  • H. Glossmann
  • C. J. Struck


The ability of ACTH fragments and of an ACTH analogue [9-tryptophan(o-nitrophenylsulfenyl)] corcicotropin-(1–24)-tetracosapeptide[Trp-(Nps)9 ACTH1–24] to stimulate adenylate cyclase in bovine adrenal cortex membranes and a crude membrane fraction from rat adrenals has been determined.

Partial agonists like Trp (Nps)9 ACTH1–24 displayed intrinsic activity in the rat adrenal preparation only if tested in the presence of 5′-guanylylimidodiphosphate [Gpp(NH)p]. On the other hand, no addition of Gpp(NH)p was necessary to demonstrate intrinsic activity of Trp(Nps)9 ACTH1–24 for bovine adrenal cortex adenylate cyclase. A large decrease (15-fold) of the apparent Km values for ACTH1–24, ACTH1–23 and ACTH1–17 was observed with the rat adrenal preparation when Gpp(NH)p was added. The shift in apparent Km values for ACTH1–24 and ACTH1–23 for the bovine adrenal cortex adenylate cyclase system was small or insignificant when Gpp(NH)p was added.

The observations suggest that the hormone receptor facilitates the action of guanylnucleotide sites in the membrane. When guanylnucleotide sites are occupied by Gpp(NH)p even weak interactions of the hormone receptor with e.g. partial agonists are propagated to the catalytic subunits of the adenylate cyclase complex resulting in enhanced activity. The differences in adenylate cyclase activation with hormone fragments or analogues and different target tissues may rather reflect the state of the coupling process involving guanylnucleotide binding sites of the isolated membrane fraction than differences in the receptor itself.

Key words

ACTH NPS-ACTH Adenylate cyclase 


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  1. Ariens, E. J.: Molecular pharmacology, Vol. 1. New York-London: Academic Press 1964Google Scholar
  2. Geiger, R.: Synthese eines Heptadecapeptides mit hoher adrenocorticotroper Wirkung. Justus Liebig's Ann. Chem. 750, 165–170 (1971)Google Scholar
  3. Geiger, R., Sturm, K., Sidel, W.: Synthese eines biologisch aktiven Tricosapeptidamids mit der Aminosäuresequenz 1–23 des Corticotropins (ACTH). Chem. Ber. 97, 1208–1213 (1964)Google Scholar
  4. Glossmann, H.: Adrenal cortex adenylate cyclase: Solubization of adenylate cyclase and guanylnucleotide binding sites. Naunyn-Schmiedeberg's Arch. Pharmacol. 291, 89–100 (1975)Google Scholar
  5. Glossmann, H., Baukal, A., Catt, K. J.: Angiotensin II receptors in bovine adrenal cortex: Modification of angiotensin II binding by guanyl nucleotides. J. biol. Chem. 249, 664–666 (1974)Google Scholar
  6. Glossmann, H., Gips, H.: Adrenal cortex adenylate cyclase: Comparison between the action of GTP and 5′-guanylyl-imidodiphosphate on the particulate enzyme from bovine adrenal cortex and rat adrenals. Naunyn-Schmiedeberg's Arch. Pharmacol. 286, 239–249 (1974)Google Scholar
  7. Glossmann, H., Gips, H.: Bovine adrenal cortex adenylate cyclase: Properties of the particulate enzyme and effects of guanylylnucleotides. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 77–97 (1975)Google Scholar
  8. Hofmann, K., Lande, S.: Improved synthetic routes to histidylphenylalanylarginyltryptophyglycine, a key intermediate in the synthesis of ACTH peptides. J. Amer. chem. Soc. 83, 2286–2289 (1961)Google Scholar
  9. Jard, S., Roy, C., Barth, T., Rajenson, R., Bockaert, J.: Antidiuretic hormone-sensitive kidney adenylatecyclase. In: Advances in cyclic nucleotide research, Vol. V (G. I. Grummond, P. Greengard, and G. Robinson, eds.), pp. 31–52. New York: Raven Press 1975Google Scholar
  10. Johnson, R. A., Pilkis, S. J., Hamet, P.: Liver membrane adenylate cyclase, synergistic effects of anions on fluoride, glucagon and guanyl nucleotide stimulation. J. biol. Chem. 250, 6599–6607 (1975)Google Scholar
  11. Kantor, H. S., Tao, P., Kiefer, H. C.: Kinetic evidence for the presence of two prostaglandin receptor sites regulating the activity of intestinal adenylate cyclase sensitive to escherichia coli enterotoxin. Proc. nat. Acad. Sci. (Wash.) 71, 1317–1321 (1974)Google Scholar
  12. Kappeler, H., Schwyzer, R.: Synthese eines Tetracosapeptides mit der Aminosäuresequenz eines hochaktiven Abbauproduktes des β-Corticotropins (ACTH) aus Schweinehypophysen. Helv. chim. Acta 46, 1550–1572 (1963)Google Scholar
  13. Londos, C., Rodbell, M.: Multiple inhibitory and activating effects of nucleotides and magnesium on adrenal adenylate cyclase. J. biol. Chem. 250, 3459–3465 (1975)Google Scholar
  14. Moyle, R. W., Kong, Y. C., Ramachandran, J.: Steroidogenesis and cyclic adenosine 3′,5′-monophophate accumulation in rat adrenal cells. Divergent effects of adrenocorticotropin and its o-nitrophenylsulfenyl derivate. J. biol. chem. 248, 2409–2417 (1973)Google Scholar
  15. Orly, J., Schramm, M.: Fatty acids as modulators of membrane functions: Catecholamine-activated adenylate cyclase of the turkey erythrocyte. Proc. nat. Acad. Sci. (Wash.) 72, 3433–3437 (1975)Google Scholar
  16. Peytreman, A., Nicholson, W. E., Brown, R. D., Liddle, G. W., Hardman, J. G.: Comparative effects of angiotensin and ACTH on cyclic AMP and steroidogenesis in isolated bovine adrenal cells. J. clin. Invest. 52, 835–842 (1973)Google Scholar
  17. Pfeuffer, T., Helmreich, E. J. M.: Activation of pigeon erythrocyte membrane adenylate cyclase by guanylnucleotide analogues and separation of a nucleotide binding protein. J. biol. Chem. 250, 867–876 (1975)Google Scholar
  18. Ramachandran, J., Lee, V.: Preparation and properties of the o-nitrophenylsulfenyl derivative of ACTH: An inhibitor of the lipolytic action of the hormone. Biochem. biophys. Res. Commun. 38, 507–512 (1970a)Google Scholar
  19. Ramachandran, J., Lee, V.: Divergent effects of o-nitrophenyl sulfenyl ACTH on rat and rabbit fat cell adenyl cyclases. Biochem. biophys. Res. Commun. 41, 358–366 (1970b)Google Scholar
  20. Rodbard, D.: Theory of Hormone—Receptor interaction. III. The endocrine target cell as a quantal response unit: A general control mechanism. In: Receptors for reproductive hormones (B. O'Malley and A. R.Means, eds.), pp. 342–364. New York: Plenum Publ. Corp. 1973Google Scholar
  21. Rodbell, M., Lin, M. C., Salomon, Y.: Evidence for interdependent action of glucagon and nucleotides on the hepatic adenylate cyclase system. J. biol. Chem. 249, 59–65 (1974)Google Scholar
  22. Rodbell, M., Lin, C. M., Salomon, Y., Londos, C., Harwood, J. P., Martin, B. R., Rendell, M., Berman, M.: Role of adenine and guanine nucleotides in the activity and response of adenylate cyclase systems to hormones: evidence for multisite transition states. In: Advances in cyclic nucleotide research, Vol. V, (G. I. Drummond, P. Greengard, and G. Robinson, eds.), pp. 3–29. New York: Raven Press 1975Google Scholar
  23. Salomon, Y., Londos, C., Rodbell, M.: A highly sensitive adenylate cyclase assay. Analyt. Biochem. 58, 541–548 (1974)Google Scholar
  24. Schramm, M., Rodbell, M.: A persistent active state of the adenylate cyclase system produced by the combined actions of isoproterenol and guanyl imidodiphosphate in frog erythrocyte membranes. J. biol. Chem. 250, 2232–2237 (1975)Google Scholar
  25. Seelig, S., Lindley, B. D., Sayers, G.: A new approach to the structure-activity relationship for ACTH analogs using isolated adrenal cortex cells. In: Methods in enzymology, Vol. 39 (J. G.Hardman and B. W. O'Malley, eds.), pp. 347–359. New York-San Francisco-London: Academic Press 1975Google Scholar
  26. Seelig, S., Sayers, G.: Isolated adrenal cortex cells: ACTH Agonists, partial agonists, antagonists; cyclic AMP and corticosterone production, Arch. Biochem. Biophys. 154, 230–239 (1973)Google Scholar
  27. Weber, E.: Grundriß der biologischen Statistik. Jena: VEB G. Fischer 1961Google Scholar
  28. Wolff, J., Cook, G. H.: Charge effects in the activation of adenylate cyclase. J. biol. Chem. 250, 6897–6903 (1975)Google Scholar

Copyright information

© Springer-Verlag 1976

Authors and Affiliations

  • H. Glossmann
    • 1
  • C. J. Struck
    • 1
  1. 1.Pharmakologisches Institut der Justus Liebig-UniversitätGießen

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