Identification of benzomorphan-kappa opiate receptors in cerebral arteries which subserve relaxation

Br J Pharmacol. 1984 Jun;82(2):459-66. doi: 10.1111/j.1476-5381.1984.tb10781.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Animals
  • Benzomorphans / analogs & derivatives
  • Benzomorphans / metabolism
  • Benzomorphans / pharmacology
  • Cerebral Arteries / drug effects*
  • Cyclazocine / analogs & derivatives
  • Cyclazocine / pharmacology
  • Dinoprost
  • Dogs
  • Drug Interactions
  • Ethylketocyclazocine
  • Female
  • In Vitro Techniques
  • Male
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects
  • Phencyclidine / pharmacology
  • Prostaglandins F / pharmacology
  • Pyrrolidines / pharmacology
  • Receptors, Opioid / analysis*
  • Receptors, Opioid, kappa

Substances

  • Benzomorphans
  • Prostaglandins F
  • Pyrrolidines
  • Receptors, Opioid
  • Receptors, Opioid, kappa
  • MR 2034
  • Ethylketocyclazocine
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • ketazocine
  • Dinoprost
  • bremazocine
  • Phencyclidine
  • Cyclazocine