Functional characterization of nonadrenergic noncholinergic neurotransmitter release via endocannabinoids: an in vitro study in rabbit corpus cavernosum.

INTRODUCTION: Corporal smooth muscle relaxation is mediated mainly but not completely by nitric oxide. Endocannabinoids modulate the various neurotransmitter systems. AIM: In the present study, a possible role of endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated relaxations was investigated. METHODS: In precontracted tissues, control electrical field stimulation (EFS)-induced NANC relaxation responses were obtained using varying frequencies of stimulation in the presence of L-arginine methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar experimental procedure was applied in the presence of cannabinoid receptor antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA), or JHW015. MAIN OUTCOME MEASURES: Effects of cannabinoid receptor antagonists and agonists on EFS-evoked non-nitrergic NANC relaxation responses. RESULTS: L-NAME abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and AM630 either together or separately inhibited, whereas anandamide, ACEA, and JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630. Capsazepine enhanced non-nitrergic NANC relaxation responses. CONCLUSION: These results suggest that non-nitrergic NANC relaxations may be mediated partially by cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and cannabinoid CB(2) receptors.

The effects of varicocele and its surgical correction on vas deferens motility.

Varicocele is the abnormal dilation of venous pampiniform plexus and internal spermatic vein. Its prevalence in the adolescent period is almost equal to the prevalence of adult age. That is why the disease is accepted to appear in early adolescence and does not disappear spontaneously. Varicocele is established to be the most common cause of infertility in the adulthood period in terms of the testicular and/or epididymal damages it causes. Besides, malfunctioning of testis and/or epididymis cannot be blamed as the one and only reason of infertility. One major reason of the male infertility is vas deferens motility disorders. There is limited data in the literature investigating the effects of varicocele on the vas deferens motility. The aim of the study is to evaluate not only the motility defects of vas deferens for the period of varicocele, but also the effects of surgical varicocele correction on vas deferens motility. Thirty male Wistar-Albino rats were allocated to five groups. In the control group (Gr C, n = 6) bilateral vas deferens strips were harvested without any surgical intervention. Using the partial left renal vein obstruction technique, the experimental varicocele model was performed for the other four groups. Varicocele was apparent for these animals after the fourth week of the venous ligation. Bilateral vas deferens strips of varicocele group (Gr V, n = 6) were harvested. The rest of the animals having varicocele underwent relaparotomies. Three different surgical procedures were performed to these animals. The animals of group P (Gr P, n = 6) and group I (Gr I, n = 6) underwent Palomo and Ivanissevich procedures, respectively, for varicocele correction. And the animals of group S (Gr S, n = 6) underwent sham operation. After 4 weeks of relaparotomies, bilateral vas deferens strips of all three groups harvested. The electrical field stimulation (EFS) induced responses of all vas deferens strips as well as exogenous drug induced responses were recorded and analysed. The results of the study showed that the varicocele significantly inhibited the first phase of biphasic response of vas deferens in the ipsilateral side. However the correction of varicocele, free from surgical technique, ameliorated the affected first phase of EFS induced biphasic response in the ipsilateral side. The results of this study suggest that varicocele can be the reason of male infertility by not only causing testicular and/or epididymal damages but also triggering vas deferens motility defects. The correction of varicocele free from surgical technique may reverse the damaging of the vas deferens. Therefore when indicated surgical correction of varicocele is essential. It seems that varicocele surgery does not only prevent late term testicular and/or epididymal damages but also avoids vas deferens motility defects.

Synthesis and calcium modulatory activity of 3-alkyloxy-carbonyl-4-(disubstituted)aryl-5-oxo-1,4,5,6,7,8-hexa-hydroquinoline derivatives.

In this study, twelve hexahydroquinoline derivatives which are condensed analogs of the 1,4-DHP molecule were synthesized and evaluated for their calcium-antagonistic activity. The results indicated that all compounds and nifedipine produced concentration-dependent relaxation in rabbit gastric fundus smooth muscle strips. The relaxant effects of the compounds on the tissues were expressed as percentage of the precontraction using Ca(2+). The maximum response (E(max)) and pD(2)values (the negative logarithm of the concentration for the half-maximal response (EC(50))) were calculated. It is generally believed that introduction of a second electron-withdrawing substituent into the phenyl ring increases the mentioned activity. Methyl-2,7,7-trimethyl-4-(2-nitro-5-chlorophenyl)-5-oxo-l,4,5,6,7,8-hexahydroquinoline-3-carboxylate 2a has been found to be the most active compound in this serie.