Effect of cholinergic agonists and antagonists on rat hypothalamic corticotropin-releasing hormone secretion in vitro.
Several lines of experimental evidence suggest that acetylcholine (ACh) is excitatory to the hypothalamic-pituitary-adrenal (HPA) axis. Since previous experiments have shown that ACh does not affect pituitary adrenocorticotropin secretion in vitro, we hypothesized that ACh stimulates the HPA axis by causing hypothalamic corticotropin-releasing hormone (CRH) secretion. We examined this hypothesis using an organ culture system that measures the ability of single rat hypothalami to secrete immunoreactive CRH (IR-rCRH) in vitro. ACh stimulated hypothalamic IR-rCRH secretion in a dose-dependent fashion, at concentrations ranging from 3.3 x 10(-10) to 10(-5) M. This effect was antagonized by the simultaneous presence of atropine and hexamethonium, a muscarinic and a nicotinic receptor antagonist, respectively (p less than 0.05). Further evidence for the cholinergic regulation of the CRH neuron was provided by the findings that both carbachol, a muscarinic receptor agonist, and nicotine, a nicotinic receptor agonist, stimulated IR-rCRH secretion in a dose-dependent fashion. These effects were antagonized by atropine and hexamethonium, respectively, suggesting that both muscarinic and nicotinic receptors are involved in the process. ACh stimulated hypothalamic IR-rCRH secretion in the presence of phentolamine, an alpha-adrenergic antagonist, and ritanserin, a serotonin2 receptor antagonist, suggesting that the cholinergic stimulation of CRH secretion is not mediated by alpha-adrenergic or serotonergic interneurons. We conclude that ACh stimulates hypothalamic CRH secretion via both muscarinic and nicotinic receptor mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D006584:Hexamethonium Compounds; D010276:Parasympatholytics; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D001285:Atropine; D003346:Corticotropin-Releasing Hormone; D000109:Acetylcholine; D010646:Phentolamine