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INTRODUCTION AND OBJECTIVE:Frailty is a key aspect, related to-but distinct from-comorbidities and age. Partial nephrectomy (PN) use has increased during the last decades. However, PN is a complex ...

INTRODUCTION AND OBJECTIVES: The endocannabinoid system modulates afferent signals under certain conditions. It is not known if the endocannabinoid-regulatory enzyme fatty acid amide hydrolase (FAAH) is located to or has a function in the ejaculatory system. We aimed to examine the expression of FAAH in the seminal vesicle and vas deferens and effects of inhibition of FAAH on seminal vesicle function and ejaculation. METHODS: After ethical approval, anesthetized male Sprague Dawley rats (250gram) were used for (I) recordings of intraluminal pressure of the seminal vesicle, or (II) pressures of the corpus spongiousum during apomorphine-induced (150 g/kg, s.c.) ejaculation. Effects by intraperitoneal oleoyl ethyl amide (OEtA; a FAAH inhibitor; 0.1, 1 and 10 mg/kg) or vehicle were studied. PCR, Western Blot and immunohistochemistry were used for studies of FAAH expression in rat and human tissues. Effect by OEtA (0.1-100 M) on isolated seminal vesicle was studied in organ baths. ANOVA and T-test were used for comparisons. RESULTS: PCR and WB demonstrated FAAH in rat and human seminal vesicles and vas deferens. FAAH was located in epithelial cells of both tissues. In human samples, the FAAH-2 isoform was similarly expressed. In isolated tissues, maximum inhibition by OEtA (100 M) on nerve-induced contractions were 21 9% (human;n 5) and 22 9% (rat;n 7). In vivo, the frequencies of spontaneous seminal vesicle contractions / min. were 1.08 0.32 (baseline) and 0.58 0.13 (OEtA 10mg/kg;p 0.05), and 1.23 0.41 (baseline) and 1.45 0.52 (vehicle; ns). OEtA increased basal pressure by 34 13% (vs. 0.3 2.9% for vehicle; p 0.05). Apomorphine-induced ejaculations were registered as suprasystolic intraspongious pressure spikes with striated muscle contractions and semen-expulsion from the urethra. Latencies to the first, second and third ejaculation were 6.0 1.2, 13.1 1.9, and 19.4 2.2 min. for vehicle (n 7); 12.7 3.2 (p 0.07), 19.6 4, and 22.8 2.6 min; and 21.8 3.3 (p 0.05) for OEtA (0.1 mg/kg; n 8), 26.9 5.1 (p 0.05), and 38.7 9.5 (p 0.05) min. for OEtA (1mg/kg; n 6). No differences in the number or pressure amplitudes of ejaculations were noted for OEtA and vehicle. CONCLUSIONS: FAAH is expressed in the rat and human vas deferens and seminal vesicle. FAAH inhibition seems to depress seminal vesicle excitability and prolongs latency for apomorphine-induced ejaculation in rats. Pharmacological targeting of FAAH may be an interesting principle to further develop in premature ejaculation.