Selective cardiovascular and neuroendocrine effects of a kappa-opioid agonist in the nucleus tractus solitarii of rats.
The cardiovascular and neuroendocrine effects of a selective kappa-opiate receptor agonist (U50488H) microinjected into the nucleus tractus solitarii have been investigated in urethane-anaesthetized rats. Comparative experiments were conducted using 8-arginine vasopressin (AVP)-deficient Brattleboro rats and an opiate agonist selective for delta receptors. Unilateral injection of U50488H elicited a significant dose-dependent increase in mean arterial pressure and a small decrease in heart rate in Sprague-Dawley rats. The pressor effect was blocked preferentially by the relatively selective kappa-receptor antagonist MR2266BS compared to naloxone. Bilateral injections of U50488H elicited a relatively greater increase in mean arterial pressure than unilateral injections and a significant decrease in heart rate. U50488H did not elicit a pressor effect in Brattleboro rats, whereas a marked response (associated with a significant increase in AVP secretion) was found in parent strain Long-Evans rats. In contrast, no such differential effects in the response of Brattleboro and Long-Evans rats were observed in parallel experiments using equimolar doses of the selective delta-opiate agonist Tyr-D-Ser-Gly-Phe-Leu-Thr which elicited a transient pressor response. An antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylene-propionic acid)2-(0-methyl) tyrosine] arginine vasopressin (1,d(CH2)5Tyr(ME)AVP) specific for the vasopressor action of AVP blocked the U50488H-induced pressor response in a dose-dependent manner when administered intravenously 10 min prior to the kappa agonist, but did not significantly attenuate the response to the delta agonist. Conversely, the U50488H-induced response was not modified by pre-treatment with phenoxybenzamine whereas the delta-agonist pressor response was completely blocked by it. The results provide evidence for specific kappa-opiate cardiovascular and neuroendocrine responses in the nucleus tractus solitarii and suggest that a kappa-receptor mechanism, possibly involving a peptide of the dynorphin group as the endogenous ligand, may operate in the central control of blood pressure and AVP secretion.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D001575:Benzomorphans / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011910:Rats, Brattleboro; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D013997:Time Factors
D001575:Benzomorphans; D009842:Oligopeptides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D010643:Phenoxybenzamine; D001127:Arginine Vasopressin; C027247:MR 2266; D004743:Enkephalin, Leucine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C025043:vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-