Thyrotropin-releasing hormone (TRH) improves survival in anaphylactic shock: a central effect mediated by the sympatho-adrenomedullary beta-adrenoceptive system.
Treatment with thyrotropin-releasing hormone (TRH) significantly improved survival following induction of fatal systemic anaphylaxis in mice. The protective effect was mediated centrally since survival was increased by intracerebroventricular (i.c.v.) administration of TRH at doses which had no effect when given systemically (5-25 micrograms). Acid-TRH, a deamidated metabolite of TRH which lacks hypophysiotropic influences, was as effective as TRH when administered i.c.v., but it was inactive following intravenous (i.v.) administration. The protective effect of TRH in anaphylaxis was reversed by treatments which diminished sympathetic outflow to the adrenal medulla, i.e. ganglionic blockade by chlorisondamine chloride or surgical denervation of the adrenal glands. Destruction of sympathetic nerve endings by the catecholamine neurotoxin 6-hydroxydopamine did not alter the response to TRH. Finally, selective blockade of beta-adrenoceptive sites by propranolol diminished the effect of TRH. Blockade of alpha-adrenoceptors by phentolamine or dopaminergic receptors by domperidone did not alter the protective effect of TRH in anaphylaxis. Collectively, these results indicate that the beneficial effect of TRH in anaphylactic shock involves central nervous system actions which are mediated peripherally through interaction of sympatho-adrenomedullary catecholamines with beta-adrenoceptive effectors. The possibility that TRH exerts its protective actions in shock by acting centrally to functionally antagonize the pathophysiologic effects of endogenous opiate peptides (endorphins) will be discussed.
D000313:Adrenal Medulla / Q000294:innervation*; D000707:Anaphylaxis / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005728:Ganglia, Sympathetic / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D011943:Receptors, Adrenergic, beta; D013973:Thyrotropin-Releasing Hormone