Central Muscarinic Receptor Subtypes Regulating Voiding in Rats

Abstract

Muscarinic receptors are distributed widely in the brain. A recent study revealed that central muscarinic receptors are involved in voiding regulation. However, to our knowledge the role of each muscarinic receptor subtype has not been resolved. Therefore, we evaluated the effect of intracerebroventricular administration of selective muscarinic M1 to M4 receptor antagonists on voiding function in rats. Female Sprague-Dawley rats were cannulated for intracerebroventricular infusion under halothane anesthesia. In experiment 1 cystometry was performed in conscious rats, and BC and maximal voiding pressure were measured. In experiment 2 a catheter was inserted via the bladder dome to the bladder neck and UPP was measured by saline infusion. Repeat cystostomy was performed, and saline infusion and discharge saline, BC, maximal IVP and minimal UPP were measured in conscious rats. Pirenzepine, methoctramine, pFHHSiD and MT-3 were used as selective M1, M2, M3 and M4 muscarinic receptor antagonists, respectively, which were injected intracerebroventricularly. In experiment 1 pirenzepine and pFHHSiD increased BC and decreased maximal voiding pressure. Methoctramine and MT-3 decreased BC. In experiment 2 pirenzepine and pFHHSiD increased BC and minimal UPP, and decreased maximal IVP. Methoctramine and MT-3 decreased BC and maximal IVP. Minimal UPP remained unchanged. Intracerebroventricular administration of muscarinic M1 and M3 receptor antagonists inhibited urination in conscious rats, while M2 and M4 receptor antagonists induced excitatory changes.