RT Journal Article T1 Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors A1 Blaha, Igor A1 Recio Visedo, María Paz A1 Martínez Sainz, María Del Pilar A1 López-Oliva Muñoz, María Elvira A1 Fernandes Ribeiro, Ana Sofía A1 Agis Torres, Ángel A1 Martínez Gómez, Ana Cristina A1 Benedito Castellote, Sara A1 García Sacristán, Albino A1 Fernandes, Vítor S. A1 Hernández Rodríguez, Medardo Vicente A2 Agustín Guerrero-Hernandez, AB Metabolic syndrome (MS) is a known risk factor for lower urinary tract symptoms. This study investigates whether functional and expression changes of cannabinoid CB1 and CB2 receptors are involved in the bladder dysfunction in an obese rat model with insulin resistance. Bladder samples from obese Zucker rat (OZR) and their respective controls lean Zucker rat (LZR) were processed for immunohistochemistry and western blot for studying the cannabinoid receptors expression. Detrusor smooth muscle (DSM) strips from LZR and OZR were also mounted in myographs for isometric force recordings. Neuronal and smooth muscle CB1 and CB2 receptor expression and the nerve fiber density was diminished in the OZR bladder. Electrical field stimulation (EFS) and acetylcholine (ACh) induced frequency- and concentration-dependent contractions of LZR and OZR DSM. ACh contractile responses were similar in LZR and OZR. EFS-elicited contractions, however, were reduced in OZR bladder. Cannabinoid receptor agonists and antagonists failed to modify the DSM basal tension in LZR and OZR In LZR bladder, EFS responses were inhibited by ACEA and SER-601, CB1 and CB2 receptor agonists, respectively, these effects being reversed by ACEA plus the CB1 antagonist, AM-251 or SER-601 plus the CB2 antagonist, AM-630. In OZR bladder, the inhibitory action of ACEA on nerve-evoked contractions was diminished, whereas that SER-601 did not change EFS responses. These results suggest that a diminished function and expression of neuronal cannabinoid CB1 and CB2 receptors, as well as a lower nerve fiber density is involved in the impaired excitatory neurotransmission of the urinary bladder from the OZR. PB San Francisco, CA : Public Library of Science SN 1932-6203 YR 2016 FD 2016 LK https://hdl.handle.net/20.500.14352/97370 UL https://hdl.handle.net/20.500.14352/97370 LA eng NO Blaha I, Recio P, Martínez MP, López-Oliva ME, Ribeiro ASF, Agis-Torres Á, et al. (2016) Impaired Excitatory Neurotransmission in the Urinary Bladder from the Obese Zucker Rat: Role of Cannabinoid Receptors. PLoS ONE 11(6): e0157424. https://doi.org/10.1371/journal.pone.0157424 NO Universidad Complutense de Madrid NO Fundação para a Ciência e a Tecnología (Portugal) DS Docta Complutense RD 9 abr 2025