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Effects of CL316,243, a β 3 ‐adrenoceptor agonist, and intravesical prostaglandin E 2 on the primary bladder afferent activity of the rat
Author(s) -
Aizawa Naoki,
Igawa Yasuhiko,
Nishizawa Osamu,
Wyndaele JeanJacques
Publication year - 2010
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.20826
Subject(s) - medicine , agonist , urinary bladder , efferent , saline , stimulation , prostaglandin e , prostaglandin , afferent , nerve fiber , endocrinology , fiber , prostaglandin e2 receptor , overactive bladder , urology , anesthesia , receptor , anatomy , chemistry , pathology , organic chemistry , alternative medicine
Aims It has been suggested that β 3 ‐adrenoceptor (β 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 β 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 Aδ‐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 µg/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 (Aδ‐fibers: n = 20, C‐fibers: n = 23) were isolated from 34 rats. Intravenous administration of CL, but not vehicle, significantly decreased Aδ‐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 Aδ‐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 β 3 ‐AR agonist, CL316,243, can inhibit the mechanosensitive Aδ‐fibers, but not the C‐fibers, of the primary bladder afferents of the rat. In addition, the β 3 ‐AR agonist can inhibit PGE 2 ‐induced C‐fiber hyperactivity. Neurourol. Urodynam. 29:771–776, 2010. © 2010 Wiley‐Liss, Inc.