Glutamatergic Mechanisms Involved in Bladder Overactivity and Pudendal Neuromodulation in Cats

• Published in: The Journal of pharmacology and experimental therapeutics 2017-07, Vol.362 (1), p.53-58
• Main Authors: Uy, Jamie, Yu, Michelle, Jiang, Xuewen, Jones, Cameron, Shen, Bing, Wang, Jicheng, Roppolo, James R, de Groat, William C, Tai, Changfeng
• Format: Article
• Language: English
• Subjects: Acetic Acid; Animals; Cats; Dizocilpine Maleate - therapeutic use; Dose-Response Relationship, Drug; Electric Stimulation; Excitatory Amino Acid Antagonists - therapeutic use; Female; Gastrointestinal, Hepatic, Pulmonary, and Renal; Glutamates; Male; Pudendal Nerve - physiopathology; Quinazolines - therapeutic use; Receptors, AMPA - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - chemically induced; Urinary Bladder, Overactive - physiopathology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.117.240895

The involvement of ionotropic glutamate receptors in bladder overactivity and pudendal neuromodulation was determined in -chloralose anesthetized cats by intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder produced bladder overactivity. In the first group of 5 cats, bladder capacity was significantly ( < 0.05) reduced to 55.3±10.0% of saline control by AA irritation. Pudendal nerve stimulation (PNS) significantly ( < 0.05) increased bladder capacity to 106.8 ± 15.0% and 106.7 ± 13.3% of saline control at 2T and 4T intensity, respectively. T is threshold intensity for inducing anal twitching. MK801 at 0.3 mg/kg prevented the increase in capacity by 2T or 4T PNS. In the second group of 5 cats, bladder capacity was significantly ( < 0.05) reduced to 49.0 ± 7.5% of saline control by AA irritation. It was then significantly ( < 0.05) increased to 80.8±13.5% and 79.0±14.0% of saline control by 2T and 4T PNS, respectively. CP465022 at 0.03-1 mg/kg prevented the increase in capacity by 2T PNS and at 0.3-1 mg/kg prevented the increase in capacity by 4T PNS. In both groups, MK801 at 0.3 mg/kg and CP465022 at 1 mg/kg significantly ( < 0.05) increased the prestimulation bladder capacity (about 80% and 20%, respectively) and reduced the amplitude of bladder contractions (about 30 and 20 cmH O, respectively). These results indicate that NMDA and AMPA glutamate receptors are important for PNS to inhibit bladder overactivity and that tonic activation of these receptors also contributes to the bladder overactivity induced by AA irritation.