Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect

  • Authors:
    • Ludwik K. Malendowicz
    • Gastone G. Nussdorfer
    • Krzysztof W. Nowak
    • Agnieszka Ziolkowska
    • Cinzia Tortorella
    • Marcin Trejter
  • View Affiliations

  • Published online on: August 1, 2003     https://doi.org/10.3892/ijmm.12.2.237
  • Pages: 237-241
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Abstract

Exendin-4 (Ex4) is a potent and long-lasting agonist of glucagon-like peptide-1 (GLP-1), which has been previously found to stimulate pituitary-adrenal axis in the rat. Aim of the present study was to gain insight into the mechanism(s) involved in the Ex4-induced rise in the rat plasma concentrations of ACTH, aldosterone and corticosterone. Preliminary time- and dose-response studies showed that the maximum stimulating effect of Ex4 occurred within 1 or 2 h and at dose ranging from 0.5 to 2.0 nmol/100 g body weight. The GLP-1 receptor (GLP-1R) antagonist Ex(9-39) did not significantly affect ACTH, aldosterone and cortico-sterone responses to Ex4. Neither the administration of CRH and arginine vasopressin (AVP)-receptor antagonists nor adrenal demedullation prevented pituitary-adrenal axis responses to Ex4. The prolonged (4 or 6 days) suppression of the pituitary ACTH release by dexamethasone impaired corticosterone, but not aldosterone response to Ex4. The following conclusions are drawn: i) Ex4 stimulates rat pituitary-adrenal axis through receptors other than the classic GLP-1R; ii) neither CRH and AVP nor medullary catecholamines are involved in the Ex4-induced stimulation of ACTH release; iii) ACTH stimulation accounts for the rise in corticosterone plasma concentration; and iv) the aldosterone secretagogue effect of Ex4 occurs via a mechanism independent of the stimulation of either ACTH or medullary catecholamines.

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August 2003
Volume 12 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Malendowicz LK, Nussdorfer GG, Nowak KW, Ziolkowska A, Tortorella C and Trejter M: Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect. Int J Mol Med 12: 237-241, 2003
APA
Malendowicz, L.K., Nussdorfer, G.G., Nowak, K.W., Ziolkowska, A., Tortorella, C., & Trejter, M. (2003). Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect. International Journal of Molecular Medicine, 12, 237-241. https://doi.org/10.3892/ijmm.12.2.237
MLA
Malendowicz, L. K., Nussdorfer, G. G., Nowak, K. W., Ziolkowska, A., Tortorella, C., Trejter, M."Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect". International Journal of Molecular Medicine 12.2 (2003): 237-241.
Chicago
Malendowicz, L. K., Nussdorfer, G. G., Nowak, K. W., Ziolkowska, A., Tortorella, C., Trejter, M."Exendin-4, a GLP-1 receptor agonist, stimulates pituitary-adrenocortical axis in the rat: Investigations into the mechanism(s) underlying Ex4 effect". International Journal of Molecular Medicine 12, no. 2 (2003): 237-241. https://doi.org/10.3892/ijmm.12.2.237