Hypothalamic receptors influencing the secretion of corticotrophin releasing hormone in the rat.

1. The production of corticotrophin releasing hormone (CRH) by the rat hypothalamus in vitro was studied in the presence and absence of various neurotransmitter substances and drugs which mimic or antagonize their actions.2. Acetylcholine, nicotine and bethanechol increased, in a dose-related manner, hypothalamic CRH release and content but the maximal responses to bethanechol or nicotine were less than those to acetylcholine.3. The actions of acetylcholine were antagonized by atropine, pempidine and hexamethonium but were completely inhibited only when atropine and pempidine were given together. The effects of nicotine were abolished by pempidine but not by atropine while those of bethanechol were abolished by atropine but not by pempidine.4. Acetylcholine-induced hypothalamic CRH activity was also antagonized by cyproheptadine but not by methysergide.5. 5-Hydroxytryptamine caused dose-related increases in hypothalamic CRH release and content. Its effects were antagonized by cyproheptadine and methysergide but not by atropine, pempidine or hexamethonium.6. Acetylcholine-induced increases in hypothalamic CRH production were reduced by GABA, noradrenaline, adrenaline, methoxamine and phenylephrine but not by isoprenaline. The actions of GABA were antagonized by bicuculline and those of noradrenaline by phentolamine but not by atenolol.7. The results suggest the presence of nicotinic and muscarinic cholinoceptors, 5-hydroxytryptamine receptors, alpha-adrenoceptors and GABA-receptors within the hypothalamus all of which may be important in the control of CRH secretion.