Effects of CL316,243, a β3-Adrenoceptor Agonist, and Intravesical Prostaglandin E2 on the Primary Bladder Afferent Activity of the Rat

Aims: It has been suggested that beta(3)-adrenoceptor (beta(3)-AR) agonists affect not only the efferent but also the afferent pathways innervating the bladder. In addition, prostaglandin E-2 (PGE(2)) causes bladder hyperactivity in conscious rats. We investigated the direct effects of a beta(3)-AR agonist (CL316,243; CL) and PGE(2) on single fiber activities of the primary bladder afferent nerves. Methods: Female Sprague-Dawley rats were used. Under urethane anesthesia, a single nerve fiber primarily originating from the bladder was identified by electrical stimulation of the left pelvic nerve and by bladder distention, and was divided by conduction velocity (2.5 m/sec) as A delta-fiber or C-fiber. The afferent activity measurements with constant bladder filling were repeated three times and the third measurement served as the base-line observation. Then, CL (10 mu g/kg) or its vehicle was administrated intravenously. Thereafter, 10(-4)M of PGE(2) or saline was instilled intravesically and another three cycles recorded. Results: Forty-three single afferent fibers (A delta-fibers: n = 20, C-fibers: n = 23) were isolated from 34 rats. Intravenous administration of CL, but not vehicle, significantly decreased A delta-fiber, but not C-fiber, activities in response to bladder filling with saline. Intravesical instillation of PGE(2) significantly increased C-fiber activities, but not A delta-fiber activities. The PGE(2)-induced increase in C-fiber activities was inhibited by pretreatment with CL. Conclusions: The present results clearly demonstrate that the beta(3)-AR agonist, CL316,243, can inhibit the mechanosensitive A delta-fibers, but not the C-fibers, of the primary bladder afferents of the rat. In addition, the beta(3)-AR agonist can inhibit PGE(2)-induced C-fiber hyperactivity. Neurourol. Urodynam. 29:771-776, 2010. (C) 2010 Wiley-Liss, Inc.