Spinal Muscarinic Recptor Subtypes Regulating Voiding In Rats

摘要

Muscarinic receptors in the central nervous system are involved in the control of voiding function. As the muscarinic receptor subtypes involved in the function of the spinal micturition reflex pathway have not yet been determined, we examined the effects of intrathecal (i.t.) administration of muscarinic Ml to M4 receptor subtype antagonists on voiding function in rats. An intrathecal administration cannula and a bladder cannula were inserted into female Sprague-Dawley rats under halothane anesthesia, and cystometry was performed in conscious animals. Bladder capacity, maximal voiding pressure (MVP), and post-void residual volume were measured, and voiding efficiency (VE) was calculated based on these values. Pirenzepine, methoctramine, p-fluorohexahydro-sila-difenidol, and tropicamide were used as Ml,M2, M3, and M4 muscarinic receptor antagonists, respectively. Although voiding parameters were not altered by 30 mug of the respective muscarinic receptor subtype antagonists, atropine at 10 mug and 30mug reduced MVP and VE. Combined administration of M2 and M4 or M2 and Ml muscarinic receptor antagonists at 30 mug reduced the VE and MVP or the VE, respectively, and that of the other two muscarinic receptor antagonists at 30|xg did not alter the micturition parameters. Combined administration of M2 and M4 or M2 and Ml muscarinic receptor antagonists arrested bladder contraction in other rats. The muscarinic receptors in the lumbosarcral micturition center are involved in facilitatory function in the voiding mechanism, but their involvement of the cholinergic system is only in part in the voiding function.