بررسي اثر سيستم كانابينوييدي اندوژن بر عملكرد عصبي بافت كوربوس كاورنوزوم دستگاه تناسلي خارجي موشهاي صحرايي نر

Effect of Edocannabinoid System on the Neurogenic Function of Rat Corpus Cavernosum

Abstract Background & Aim: Although studies have shown the central effects of Endocannabinoid on erection, itsʹ peripheral effect is unknown. The purpose of this study was to investigate the effect of the endogenous cannabinoid anandamide on the nonadrenergic noncholinergic(NANC) relaxant responses to electrical field stimulation in isolated rat corpus cavernosum, a crucial tissue in erectile function. Material and Methods: The rat corporeal strips were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate(5 \iM) and atropine(l nM)(to produce adrenergic and cholinergic blockade). The strips were precontracted with phenylephrine hydrochloride(7.5 nM) and electrical field stimulation was applied at different frequencies(2, 5, 10, 15 Hz) to obtain NANC-mediated relaxation. Anandamide(0.3, 1 and 3 nM in separate groups) was added 20-rnin before electrical stimulation. In another group, the selective cannabinoid CB1 receptor antagonist AM251(1 nM), the selective cannabinoid CB2 receptor antagonist AM630(1 ^M) and a variilloid receptor antagonist capsazepine(3 ^M) were separately added to the bathing medium 45-min before anandamide(l jiM) administration. Using western blotting, the existence of cannabinoid and variilloid receptors were assessed in this tissue. Each group consisted of six rats. This study was an experimental study. Statistical analysis of the data was performed by one-way analysis of variance(ANOVA) followed by Newman-keuls post hoc test. Statistical significance was considered when P<0.05. Results: The results showed that the NANC relaxant responses were significantly enhanced in the presence of anandamide at 1 and 3 nM. The potentiating effect of anandamide(l jiM) on relaxation responses was significantly lessened by either AM251(1 \iM) or capsazepine(3 jiM), but not by AM630(1 nM)(P<0.01). Neither of these antagonists had influence on relaxation responses. Preincubation with the nitric oxide synthase inhibitor L-NAME(1 nM) significantly inhibited the relaxation responses in the presence or absence of 1 ^M anandamide(P<0.001). Although at 30 nM, L-NAME did not influence NANC responses, it significantly reduced(P<0.01) the attenuating effect of anandamide on NANC responses. Anandamide(l nM)) had no influence on concentration-dependent relaxant responses to sodium nitroprusside(10nM- ImM), an NO donor. Western blotting revealed the existence of cannabinoid CBl(but not CB2) and vanilloid VR1 receptors in rat corpus cavernosum. Conclusion: For the first time, our results indicated the potentiating activity of anandamide on NANC-mediated relaxation of rat corpus cavernosum through both CB1 and vanilloid receptors. The NO-mediated component of the NANC relaxant responses to electrical stimulation is involved in this enhancement. Also it was shown that CB1 and VR1 receptors are present in this tissue.