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
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Adenosine Triphosphate / pharmacology*
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Adrenergic alpha-Antagonists / pharmacology
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Animals
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Benzoxazines
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Electric Stimulation
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Epididymis
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Male
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Morpholines / pharmacology*
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Muscle Contraction / drug effects
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Muscle, Smooth / drug effects
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Muscle, Smooth / physiology
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Naphthalenes / pharmacology*
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Piperidines / pharmacology
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Prazosin / pharmacology
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Prostate
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Pyrazoles / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Cannabinoid, CB1 / agonists
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors
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Receptor, Cannabinoid, CB1 / physiology*
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Receptors, Presynaptic / agonists
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Receptors, Presynaptic / antagonists & inhibitors
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Receptors, Presynaptic / physiology
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Vas Deferens / drug effects
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Vas Deferens / innervation*
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Vas Deferens / physiology
Substances
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Adrenergic alpha-Antagonists
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Benzoxazines
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Morpholines
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N-piperidinyl-(8-chloro-1-(2,4-dichlorophenyl)-1,4,5,6-tetrahydrobenzo(6,7)cyclohepta(1,2-c)pyrazole-3-carboxamide)
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Naphthalenes
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Receptors, Presynaptic
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(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
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Adenosine Triphosphate
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Prazosin