Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors

Eur J Pharmacol. 2005 Nov 21;525(1-3):150-3. doi: 10.1016/j.ejphar.2005.09.058. Epub 2005 Nov 3.

Abstract

The effect of R-(+)-[2,3-dihydro-5-methyl-3-[(morpholiny)methyl]pyrolol[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)methanone mesylate (WIN 55,212-2; a cannabinoid receptor agonist) was investigated on contractions of the bisected (epididymal and prostatic portions) rat vas deferens to assess the role of cannabinoid receptors in sympathetic ATP neurotransmission. WIN 55,212-2 inhibited the electrically induced contractions in both portions of the rat vas deferens. In the presence of the alpha1-adrenoreceptor antagonist prazosin, electrical stimulation produces a contraction mediated exclusively by ATP. In this condition, WIN 55,212-2 in the prostatic portion elicited a concentration-dependent inhibition that was antagonized by N-piperidinyl-[8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo[6,7]cyclohepta[1,2-c]pyrazole-3-carboxamide] (NESS 0327), a selective cannabinoid CB1 receptor antagonist. NESS 0327 caused a parallel dextral displacement of the WIN 55,212-2 concentration-response curve. It is suggested that activation of pre-junctional cannabinoid receptors on sympathetic nerves of the vas deferens modulates ATP neurotransmission.

MeSH terms

  • Adenosine Triphosphate / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Benzoxazines
  • Electric Stimulation
  • Epididymis
  • Male
  • Morpholines / pharmacology*
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Naphthalenes / pharmacology*
  • Piperidines / pharmacology
  • Prazosin / pharmacology
  • Prostate
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB1 / agonists
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / physiology*
  • Receptors, Presynaptic / agonists
  • Receptors, Presynaptic / antagonists & inhibitors
  • Receptors, Presynaptic / physiology
  • Vas Deferens / drug effects
  • Vas Deferens / innervation*
  • Vas Deferens / physiology

Substances

  • Adrenergic alpha-Antagonists
  • Benzoxazines
  • Morpholines
  • N-piperidinyl-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo(6,7)cyclohepta(1,2-c)pyrazole-3-carboxamide)
  • Naphthalenes
  • Piperidines
  • Pyrazoles
  • Receptor, Cannabinoid, CB1
  • Receptors, Presynaptic
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Adenosine Triphosphate
  • Prazosin