Modulation of ATP-mediated contractions of the rat vas deferens through presynaptic cannabinoid receptors.
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.
Tambaro
Simone
S
Neuroscienze-PharmaNess S.c.ar.l, Via Palabanda 9, 09124 Cagliari, Italy. simone.tambaro@pharmaness.it
Mongeau
Raymond
R
Dessi
Christian
C
Pani
Luca
L
Ruiu
Stefania
S
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D004558:Electric Stimulation; D004822:Epididymis; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011467:Prostate; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation* / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D048588:Benzoxazines; D009025:Morpholines; C475771:N-piperidinyl-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo(6,7)cyclohepta(1,2-c)pyrazole-3-carboxamide); D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D017661:Receptors, Presynaptic; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000255:Adenosine Triphosphate; D011224:Prazosin