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.