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The muscarinic cholinergic agonist arecoline stimulates the rat hypothalamic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism.
Endocrinology. 1989 Nov; 125(5):2445-53.E

Abstract

Several lines of experimental evidence suggest that acetylcholine and other cholinergic agonists are excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. To examine the site on the HPA axis that is stimulated by cholinergic agents, we evaluated the in vivo and in vitro effects of the muscarinic cholinergic agonist arecoline in intact and pituitary stalk-transected rats as well as on isolated rat hypothalami, dispersed anterior pituicytes, and adrenocortical cells in culture. Arecoline, injected iv to catheterized, freely moving male Sprague-Dawley rats, stimulated plasma ACTH and corticosterone release in a dose-dependent fashion. The muscarinic cholinergic antagonist atropine significantly blunted the ACTH response to arecoline. Pituitary stalk transection led to diminished plasma ACTH and corticosterone responses to arecoline. Similarly, previous administration of anti-CRH serum significantly blunted these responses. These findings suggest that arecoline stimulates the HPA axis centrally, mainly via secretion of CRH. This hypothesis was confirmed by the dose-dependent ability of arecoline to cause hypothalamic CRH secretion in vitro, an effect antagonized by atropine, and its failure to elicit ACTH and corticosterone secretion by dispersed anterior pituicytes and adrenocortical cells in culture, respectively. These data suggest that the muscarinic cholinergic agonist arecoline stimulates the HPA axis in the rat and that this effect is mediated mainly by the release of endogenous CRH. Arecoline, therefore, appears to be a compound suitable to selectively evaluate the responsiveness of the central component of the HPA axis.

Authors+Show Affiliations

Development Endocrinology Branch, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

2551652

Citation

Calogero, A E., et al. "The Muscarinic Cholinergic Agonist Arecoline Stimulates the Rat Hypothalamic-pituitary-adrenal Axis Through a Centrally-mediated Corticotropin-releasing Hormone-dependent Mechanism." Endocrinology, vol. 125, no. 5, 1989, pp. 2445-53.
Calogero AE, Kamilaris TC, Gomez MT, et al. The muscarinic cholinergic agonist arecoline stimulates the rat hypothalamic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism. Endocrinology. 1989;125(5):2445-53.
Calogero, A. E., Kamilaris, T. C., Gomez, M. T., Johnson, E. O., Tartaglia, M. E., Gold, P. W., & Chrousos, G. P. (1989). The muscarinic cholinergic agonist arecoline stimulates the rat hypothalamic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism. Endocrinology, 125(5), 2445-53.
Calogero AE, et al. The Muscarinic Cholinergic Agonist Arecoline Stimulates the Rat Hypothalamic-pituitary-adrenal Axis Through a Centrally-mediated Corticotropin-releasing Hormone-dependent Mechanism. Endocrinology. 1989;125(5):2445-53. PubMed PMID: 2551652.
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TY - JOUR T1 - The muscarinic cholinergic agonist arecoline stimulates the rat hypothalamic-pituitary-adrenal axis through a centrally-mediated corticotropin-releasing hormone-dependent mechanism. AU - Calogero,A E, AU - Kamilaris,T C, AU - Gomez,M T, AU - Johnson,E O, AU - Tartaglia,M E, AU - Gold,P W, AU - Chrousos,G P, PY - 1989/11/1/pubmed PY - 1989/11/1/medline PY - 1989/11/1/entrez SP - 2445 EP - 53 JF - Endocrinology JO - Endocrinology VL - 125 IS - 5 N2 - Several lines of experimental evidence suggest that acetylcholine and other cholinergic agonists are excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. To examine the site on the HPA axis that is stimulated by cholinergic agents, we evaluated the in vivo and in vitro effects of the muscarinic cholinergic agonist arecoline in intact and pituitary stalk-transected rats as well as on isolated rat hypothalami, dispersed anterior pituicytes, and adrenocortical cells in culture. Arecoline, injected iv to catheterized, freely moving male Sprague-Dawley rats, stimulated plasma ACTH and corticosterone release in a dose-dependent fashion. The muscarinic cholinergic antagonist atropine significantly blunted the ACTH response to arecoline. Pituitary stalk transection led to diminished plasma ACTH and corticosterone responses to arecoline. Similarly, previous administration of anti-CRH serum significantly blunted these responses. These findings suggest that arecoline stimulates the HPA axis centrally, mainly via secretion of CRH. This hypothesis was confirmed by the dose-dependent ability of arecoline to cause hypothalamic CRH secretion in vitro, an effect antagonized by atropine, and its failure to elicit ACTH and corticosterone secretion by dispersed anterior pituicytes and adrenocortical cells in culture, respectively. These data suggest that the muscarinic cholinergic agonist arecoline stimulates the HPA axis in the rat and that this effect is mediated mainly by the release of endogenous CRH. Arecoline, therefore, appears to be a compound suitable to selectively evaluate the responsiveness of the central component of the HPA axis. SN - 0013-7227 UR - https://www.unboundmedicine.com/medline/citation/2551652/The_muscarinic_cholinergic_agonist_arecoline_stimulates_the_rat_hypothalamic_pituitary_adrenal_axis_through_a_centrally_mediated_corticotropin_releasing_hormone_dependent_mechanism_ L2 - https://academic.oup.com/endo/article-lookup/doi/10.1210/endo-125-5-2445 DB - PRIME DP - Unbound Medicine ER -