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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, OBJECTIVE, METHODS, METHODS, METHODS. Meshes: Animals, Benzhydryl Compounds, Cholinergic Agonists, Cholinergic Antagonists, Cholinergic Neurons, Female, Infusion Pumps, Implantable, Mandelic Acids, Muscle Contraction, Purinergic P2X Receptor Agonists, Purinergic P2X Receptor Antagonists, Purines, Rats, Rats, Wistar, Receptor, Muscarinic M2, Receptor, Muscarinic M3, Receptors, Muscarinic, Receptors, Purinergic P2X1, Synaptic Transmission, Time Factors, Urinary Bladder, Urinary Catheterization, Urination, Urodynamics, Urological Agents.
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Does chronic administration of anticholinergics in rats induce a shift from muscarinic to purinergic transmission in the bladder wall? Context: First-line pharmacotherapy for overactive bladder consists of anticholinergics. However, patient compliance is exceptionally low, which may be due to progressive loss of effectiveness. To decipher the involved molecular mechanisms and to evaluate the effects of chronic systemic administration of anticholinergics on bladder function and on muscarinic and purinergic receptors expression in rats. Female Wistar rats were implanted with an osmotic pump that chronically administered vehicle (Vehc), 0.36 mg/kg per day oxybutynin (Oxyc), or 0.19 mg/kg per day fesoterodine (Fesoc) for 28 d. For cystometry experiments, a small catheter was implanted in the bladder. Urologic phenotype was evaluated by the analysis of the micturition pattern and urodynamics. Expression of muscarinic and purinergic receptors was assessed by Western blot analysis of detrusor membrane protein. Functional responses to carbachol and adenosine triphosphate (ATP) were evaluated using muscle-strip contractility experiments.
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The number of voided spots was transiently decreased in Oxyc rats. In Oxyc rats, the effect of an acute high dose of oxybutynin (1mg/kg intraperitoneally [IP]) on the intermicturition interval was abolished. Expression experiments revealed a decrease of muscarinic acetylcholine receptors M2 (mAChR2) and M3 (mAChR3), whereas the purinergic receptor P2X, ligand-gated ion channel, 1 (P2X1) was enhanced in Oxyc and Fesoc rats compared to Vehc rats. In concordance with the modification of the expression pattern in Oxyc rats, the force generated by carbachol and ATP in muscle-strip contractility experiments was, respectively, lower and higher. Urodynamics revealed that the effects of systemic administration of the purinergic blocker pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (50mg/kg IP) were enhanced in Oxyc rats. As rat bladder physiology is different from that of humans, it is difficult to directly extrapolate our findings to human patients. Final Decision: yes