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Vol. 297, Issue 3, 933-939, June 2001

Central Muscarinic Mechanisms Regulating Voiding in Rats

Yoshiyuki Ishiura , Mitsuharu Yoshiyama, Osamu Yokoyama , Mikio Namiki and William C. de Groat

Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Y.I., M.Y., O.Y., W.C.deG.); and Department of Urology, Kanazawa University School of Medicine, Kanazawa, Japan (Y.I., O.Y., M.N.)

The influence of muscarinic receptor stimulation and blockade on the central regulation of micturition was evaluated in conscious female rats. Saline was infused into the bladder to induce repeated bladder contractions and voiding. Increasing doses of a muscarinic agonist, oxotremorine-M (OXO-M; 0.01 to 1 µg/rat) or antagonist, atropine (0.1 to 30 µg/rat) were administered. Intrathecal OXO-M (0.1 µg) increased bladder capacity (BC; 85 ± 17%), but did not change maximal voiding pressure (MVP), pressure threshold (PT), postvoiding intravesical pressure, or voiding efficiency (VE). Intracerebroventricular OXO-M (0.1 µg) increased BC (97 ± 6%), MVP (45 ± 19%), PT (158 ± 49%), and reduced VE (-17 ± 5%). A larger dose of OXO-M (1 µg, either i.c.v. or i.t.) produced greater changes. These effects were not reproduced by i.v. injections of OXO-M. The effects of OXO-M were blocked by pretreatment with atropine in a dose (1 µg i.c.v. or i.t.), which alone had no effect on voiding parameters. A larger dose of atropine (10 µg) reduced MP (-31 ± 7% i.c.v. and -34 ± 6% i.t.) and VE (-21 ± 3% i.c.v. and -25 ± 5% i.t.) but increased BC (52 ± 8% i.c.v.). These results indicate that activation of muscarinic receptors in the brain or spinal cord can suppress voluntary voiding, but also stimulates bladder activity during bladder filling. The muscarinic inhibitory mechanisms do not appear to be tonically active. The effects of atropine (i.c.v. and i.t.) indicate that muscarinic excitatory mechanisms are tonically active. These findings raise the possibility that voiding function is regulated by both inhibitory and excitatory cholinergic mechanisms in the central nervous system.

0022-3565/01/2973-0933$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


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