MP43-08 INHIBITION OF PERIPHERAL FATTY ACID AMIDE HYDROLASE (FAAH) INCREASES LATENCY TO EJACULATION IN RATS

Abstract

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Basic Research I1 Apr 2014MP43-08 INHIBITION OF PERIPHERAL FATTY ACID AMIDE HYDROLASE (FAAH) INCREASES LATENCY TO EJACULATION IN RATS Luca Boeri, Giovanni La Croce, Fabio Castiglione, Fabio Benigni, Francesco Mistretta, Marteen Albersen, Francesco Montorsi, Francois Giuliano, and Petter Hedlund Luca BoeriLuca Boeri More articles by this author , Giovanni La CroceGiovanni La Croce More articles by this author , Fabio CastiglioneFabio Castiglione More articles by this author , Fabio BenigniFabio Benigni More articles by this author , Francesco MistrettaFrancesco Mistretta More articles by this author , Marteen AlbersenMarteen Albersen More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , Francois GiulianoFrancois Giuliano More articles by this author , and Petter HedlundPetter Hedlund More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1165AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives We recently located the endocannabinoid-regulatory enzyme fatty acid amide hydrolase (FAAH) in the human and rat ejaculatory system, but the role for peripheral FAAH-signals in ejaculatory function is not known. URB937 is a novel FAAH inhibitor that is impermeable to the central nervous system and is restricted to act at peripheral sites. We aimed to study effects by URB937 on ejaculatory responses in rats. Methods After ethical approval, anesthetized Sprague Dawley rats (250gram) and received a catheter in the corpus spongiousum for pressure-registration during apomorphine-induced ejaculatory responses. Rats were pre-treated (30 minutes) with vehicle or URB937 (0.1 or 1 mg/kg; intraperitoneal) before apomorphine (150μg/kg, subcutaneous). Data are given as mean±SEM. Comparisons to vehicle are made with an ANOVA (Student Newman-Keuls). Results Ejaculatory responses to apomorphine were recorded as rapid intraspongious suprasystolic pressure spikes that were also observed with striated penile muscle contractions and expulsion of semen from the urethra. During the observation period (60 min), 3.8±0.4 (vehicle) or 3.0±0.4 (both URB937 0.1 or 1mg/kg) ejaculatory responses were recorded. The latency to the first (T1), second (T2) and third (T3) ejaculatory responses were 4.1±0.8, 9.3±1.1, and 15.4±1.5 minutes for vehicle (n=12). In comparison, T1, T2 and T3 in URB937-treated rats (0.1 mg/kg; n=6) amounted to 13.2±2.6, 26.4±6.3, 32.6±10.4 minutes (all p<0.05). After 1 mg/kg of URB937 (n=7), T1, T2 and T3 were 15.1±4.3, 23.9±4.8, 25.7±1.7 minutes (all p<0.05). The inter-ejaculatory time for vehicle was 5.2±0.8 minutes. Corresponding values for URB937 was 9.6±2.2 (0.1mg/kg; p<0.05) and 8.1±1.0 minutes (1mg/kg; p=0.07). URB937 did not prolong the duration of ejaculatory responses / intraspongious pressure spikes. No differences in basal intraspongious pressures were recorded between groups (34 to 36 cmH2O) and intraspongious pressure amplitudes during ejaculatory responses reached 158±16 (vehicle), 163±16 (URB937 0.1mg/kg), and 136±20 cmH2O (URB937 1mg/kg). The area under the pressure curve amounted to 63±8 (vehicle), 65±8 (URB937 0.1mg/kg), and 59±3 cmH2O/s (URB937 1mg/kg). Conclusions The prolonged latency to apomorphine-induced ejaculatory responses with URB937 is, based on the compound's pharmacological profile, suggested to involve peripheral regulatory endocannabinoid signals. FAAH may be an interesting drug target to further study in premature ejaculation. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e479-e480 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Luca Boeri More articles by this author Giovanni La Croce More articles by this author Fabio Castiglione More articles by this author Fabio Benigni More articles by this author Francesco Mistretta More articles by this author Marteen Albersen More articles by this author Francesco Montorsi More articles by this author Francois Giuliano More articles by this author Petter Hedlund More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...