Summary
The lipolytic action of natural porcine ACTH1–39 and of a number of highly purified synthetic ACTH peptide fragments was studied using rat adipocytes. Of the analogues tested, only ACTH1–24 exhibited full lipolytic activity with respect to intrinsic activity and affinity. Several shorter fragments appeared to be full agonists but had lower affinity. Fragments ACTH5–10 and ACTH7–10 were inactive. No antagonistic effects against the lipolytic action of ACTH could be demonstrated with substimulatory doses of ACTH1–16, ACTH1–10, ACTH7–24 and ACTH11–24. Based on the relative potency derived from dose-response curves, a more refined model with respect to the active centers being encoded in various sequences of the hormone, is proposed.
Similar content being viewed by others
References
Ariëns, E. J.: Drug receptor interactions: Interaction of one or more drugs with one receptor system. In: Molecular pharmacology: The mode of action of biologically active compounds (E. J. Ariëns, ed.), pp. 119–286. New York: Academic Press 1964
Bär, H. P., Hechter, O., Schwartz, I. L., Walter, R.: Neurohypophyseal hormone-sensitive adenyl-cyclase of toad urinary bladder. Proc. Natl. Acad. Sci. U.S.A.67, 7 (1970)
Beall, R. J., Sayers, G.: Isolated adrenal cells: steroidogenesis and cyclic AMP accumulation in response to ACTH. Arch. Biochem. Biophys.148, 70–76 (1972)
Blake, J., Li, C. H.: Adrenocorticotropin. Synthesis of (6-phenylalanine)-α1–19-adrenocorticotropic hormone and its steroidogenic, melanocyte-stimulating, and lipolytic activity. Biochemistry11, 3459–3461 (1972)
Braun, T., Hechter, O.: Comparative study of hormonal regulation of adenyl cyclase activity in rat and rabbit fat cell membranes. In: Adipose Tissue, regulation and metabolic functions (Jeanrenaud, B., and Hepp, D., eds.), pp. 11–19. Stuttgart: G. Thieme 1971
Chen, R. F.: Removal of fatty acids from serum albumin by charcoal treatment. J. Biol. Chem.242, 173–181 (1967)
De Wied, D.: Pituitary-adrenal system hormones and behavior. In: Neurosciences, Third Study Program (Schmitt, F. O., Worden, F. G., eds.), pp. 653–666. Cambridge: MIT Press 1974
De Wied, D., Witter, A., Greven, H. M.: Commentary: Behaviourally active ACTH analogues. Biochem. Pharmacol.24, 1463–1468 (1975)
Draper, M. W., Merrifield, R. B., Rizack, M. A.: Lipolytic activity of Met-Arg-His-Phe-Arg-Trp-Gly, a synthetic analog of the ACTH (4–10) core sequence. J. Med. Chem.16, 1326–1330 (1973)
Eggena, P., Schwartz, I. L., Walter, R.: Treshold and receptor reserve in the action of neurohypophyseal peptides. A study of synergists and antagonists of the hydroosmotic response of the toad urinary bladder. J. Gen. Physiol.56, 250 (1970)
Glossmann, H., Struck, C. J.: Adrenal cortex adenylate cyclase. In vitro activity of ACTH fragments and analogues. Naunyn-Schmiedeberg's Arch. Pharmacol.294, 199–206 (1976)
Greven, H. M., De Wied, D.: The influence of peptides derived from Corticotropin (ACTH) on performance. Structure activity studies. In: Progress in brain research (Zimmermann, E., Gispen, W. H., Marks, B. H., De Wied, D., eds.), vol. 39, pp. 429–442. Amsterdam: Elsevier 1973
Greven, H. M., De Wied, D.: Influence of peptides structurally related to ACTH and MSH on active avoidance behaviour in rats. In: Frontiers of hormone research (van Wimersma Greidanus, Tj. B., ed.), vol. 4, pp. 140–152. Basel: S. Karger 1977
Hechter, O., Braun, T.: Peptide hormone-receptor interaction: an informational transaction. In: Structure-activity relationships of protein and polypeptide hormones. Part I, (Margoulies, M., Greenwood, F. C., eds.), pp. 212–227. Amsterdam: Exerpta Med. 1971
Hofmann, K.: Preliminary observations relating structure and function in some pituitary hormones. Brookhaven Symp. Biol.13, 184–202 (1960)
IUPAC-IUB, Commission on Biochemical Nomenclature: Abbreviated designation of amino acid derivatives and peptides. Tentative rules. Eur. J. Biochem.1, 375–378 (1967)
Kappeler, H., Schwyzer, R.: Die Synthese eines Tetracosapeptides mit der Aminosäuresequenz eines hochaktiven Abbauproduktes des β-ACTH aus Schweinehypophysen. Helv. Chim. Acta44, 1136–1141 (1961)
Lang, U., Karlaganis, G., Vogel, R., Schwyzer, R.: Hormone-receptor interactions. Hormone binding site increase in isolated fat cells by phenoxazones. Biochemistry13, 2626–2633 (1974)
Li, C. H., Oelofsen, W.: Remarks on the basic core of ACTH. In: The adrenal cortex (Eisenstein, A. B., ed.), pp. 196–199. Boston, Mass.: Little, Brown and Co., 1967
Nispen, J. W. van, Tesser, G. I., Barthe, P. L., Maier, R., Schenkel-Hulliger, L.: Biological activities of ACTH-analogues varied in the active site. Acta Endocrin.84, 470–484 (1977)
Noma, A., Okabe, H., Kita, M.: A new colorimetric microdetermination of free fatty acids in serum. Clin. Chim. Acta43, 317–320 (1973)
Opmeer, F. A., Dinnendahl, V., Stock, K.: Catecholamine-induced lipolysis: Only via cyclic AMP? Biochem. Pharmacol.25, 1481–1484 (1976)
Ramachandran, J.: The structure and function of adrenocorticotropin. In: Hormonal proteins and peptides (Li, C. H., ed.), pp. 1–28, New York: Academic Press 1973
Robison, G. A., Butcher, R. W., Sutherland, E. W.: Lipolysis in adipose tissue. In: Cyclic AMP (Robison, G. A., Butcher, R. W., Sutherland, E. W., eds.), pp. 285–316. New York-London: Academic Press 1971
Rodbell, M.: Metabolism of isolated fat cells. J. Biol. Chem.242, 375–380 (1964)
Rodbell, M.: Modulation of lipolysis in adipose tissue by fatty acid centration in fat cells. Ann. N.Y. Acad. Sci.131, 302–314 (1965)
Seelig, S., Sayers, G., Schwyzer, R., Schiller, P.: Isolated adrenal cells: ACTH11–24, a competitive antagonist of ACTH1–39 and ACTH1–10. FEBS Letters19, 232–234 (1971)
Seelig, S., Lindley, B. D., Sayers, G.: A new approach to the structure-activity relationship for ACTH analogus using isolated adrenal cortex cells. In: Methods in enzymology, vol. 39 (Hardman, J. G., O'Malley, B. W., eds.), pp. 347–359. New York-San Francisco-London: Academic Press 1975
Schwyzer, R.: Molecular mechanism of polypeptide hormone action. In: Peptides 1972, Proc. 12th Eur. Peptide Symp. (Hanson and Jakubke, eds.), pp. 424–436. Amsterdam: North-Holland 1973
Schwyzer, R., Eberle, A.: On the molecular mechanism of α-MSH-receptor interactions. In: Frontiers of hormone research (van Wimersma Greidanus, Tj. B., ed.), vol. 4. Basel: S. Karger 1977
Schwyzer, R., Schiller, P., Seelig, S., Sayers, G.: Isolated adrenal cells: log dose response curves for steroidogenesis induced by ACTH1–24, ACTH1–10, ACTH4–10 and ACTH5–10. FEBS Letters19, 229–231 (1971)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Opmeer, F.A., Van Ree, J.M. & De Wied, D. ACTH-Induced lipolysis in rat adipocytes: Structure-activity relationships. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 31–36 (1978). https://doi.org/10.1007/BF00586593
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00586593