Muscarinic involvement in the regulation of gonadotropin-releasing hormone in the cyclic rat.
The release of gonadotropin-releasing hormone (GnRH) from the median eminence (ME) in cyclic rats was stimulated to a significant extent by the selective muscarinic antagonists 11[(2)(diethylamino)methyl][-1-piperidinyl]-acetyl-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX-116) and methoctramine, and to a lesser extent also by other ligands selectively antagonistic to m1 and m3 receptors. Such stimulation was estrous-cycle-dependent and was not achieved by muscarinic agonists. We suggest that the effect is induced via the m4 receptor subtype. Attempts to block the muscarinic-antagonist-induced stimulation of GnRH release with a variety of drugs were successful only in the presence of prazosin, an antagonist to alpha 1-adrenergic receptors. One possible explanation for this muscarinically mediated stimulation of GnRH release is that it results from cross-talk between the muscarinic and the alpha 1-adrenergic receptors, i.e., muscarinic agonists might inhibit the release induced by alpha 1-agonists, and muscarinic antagonists, by cancelling this inhibitory effect, might thus allow the endogenous alpha 1-agent, norepinephrine, to induce the release of GnRH.
Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
D
D
Koren
Y
Y
Egozi
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Sokolovsky
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D003959:Diamines / Q000494:pharmacology; D004971:Estrus; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D008473:Median Eminence / Q000187:drug effects / Q000378:metabolism*; D018727:Muscarinic Antagonists; D009638:Norepinephrine / Q000502:physiology; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology; D011976:Receptors, Muscarinic / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D012636:Secretory Rate / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D003959:Diamines; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D012702:Serotonin Antagonists; D007987:Gonadotropin-Releasing Hormone; D010890:Pirenzepine; C054938:methoctramine; C048593:otenzepad; D009638:Norepinephrine