1021 INHIBITION OF THE FATTY ACID AMIDE HYDROLASE INCREASES LATENCY TO APOMORPHINE-INDUCED EJACULATION IN RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research (II)1 Apr 20131021 INHIBITION OF THE FATTY ACID AMIDE HYDROLASE INCREASES LATENCY TO APOMORPHINE-INDUCED EJACULATION IN RATS Giovanni La Croce, Arianna Bettiga, Roberta Buono, Giorgia Colciago, Fabio Benigni, Francesco Mistretta, Francesco Montorsi, Fabio Castiglione, Maarten Albersen, and Petter Hedlund Giovanni La CroceGiovanni La Croce Milan, Italy More articles by this author , Arianna BettigaArianna Bettiga Milan, Italy More articles by this author , Roberta BuonoRoberta Buono Milan, Italy More articles by this author , Giorgia ColciagoGiorgia Colciago Milan, Italy More articles by this author , Fabio BenigniFabio Benigni Milan, Italy More articles by this author , Francesco MistrettaFrancesco Mistretta Milan, Italy More articles by this author , Francesco MontorsiFrancesco Montorsi Milan, Italy More articles by this author , Fabio CastiglioneFabio Castiglione Milan, Italy More articles by this author , Maarten AlbersenMaarten Albersen Leuven, Belgium More articles by this author , and Petter HedlundPetter Hedlund Milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.606AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail 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 (150μg/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 μM) 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 μM) 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. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e419 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Giovanni La Croce Milan, Italy More articles by this author Arianna Bettiga Milan, Italy More articles by this author Roberta Buono Milan, Italy More articles by this author Giorgia Colciago Milan, Italy More articles by this author Fabio Benigni Milan, Italy More articles by this author Francesco Mistretta Milan, Italy More articles by this author Francesco Montorsi Milan, Italy More articles by this author Fabio Castiglione Milan, Italy More articles by this author Maarten Albersen Leuven, Belgium More articles by this author Petter Hedlund Milan, Italy More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...