Identification of benzomorphan-kappa opiate receptors in cerebral arteries which subserve relaxation.
Several 'so-called' kappa-opiate receptor agonists e.g., ketocyclazocine (Kc), ethylketocyclazocine (Ekc), bremazocine, MR-2034 and U-50488H, were tested on basilar and middle cerebral arteries of the dog in vitro for relaxant or contractile activities. Ekc, Kc and bremazocine were found to produce concentration-dependent reductions in basal tone and to relax cerebral arteries contracted with prostaglandin F2 alpha (PGF2 alpha). All three agonists appear to act on benzomorphan-kappa opiate receptors which subserve relaxation in cerebral blood vessels. MR-2034 and U-50488H were found to induce contraction in the cerebral arteries. These opiate agonists appear to act on phencyclidine (PCP) or sigma-opiate receptors which subserve contraction. A variety of pharmacological antagonists (phentolamine, propranolol, methysergide, atropine, diphenhydramine, cimetidine, naloxone) did not modify any of the cerebral vascular effects produced by the opiates. These results suggest: (1) specific benzomorphan-kappa opiate receptors which subserve relaxation exist in cerebral blood vessels; (2) some kappa agonists appear to produce, primarily, contraction in cerebral vessels via PCP or sigma-opiate receptors: and cerebral vascular muscle may provide a useful tool to analyse the molecular constitution of these two distinct and opposite-acting opiate receptors.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001575:Benzomorphans / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D015237:Dinoprost; D004285:Dogs; D004347:Drug Interactions; D016314:Ethylketocyclazocine / Q000031:analogs & derivatives; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011957:Receptors, Opioid / Q000032:analysis*; D017473:Receptors, Opioid, kappa
D001575:Benzomorphans; D011460:Prostaglandins F; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C032478:MR 2034; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C012395:ketazocine; D015237:Dinoprost; C027248:bremazocine; D010622:Phencyclidine; D003496:Cyclazocine