Effects of CL316,243, a β3-adrenoceptor agonist, and intravesical prostaglandin E2 on the primary bladder afferent activity of the rat

Authors


  • Conflicts of interest: none.

  • Karl-Erik Andersson led the review process.

Abstract

Aims

It has been suggested that β3-adrenoceptor (β3-AR) agonists affect not only the efferent but also the afferent pathways innervating the bladder. In addition, prostaglandin E2 (PGE2) causes bladder hyperactivity in conscious rats. We investigated the direct effects of a β3-AR agonist (CL316,243; CL) and PGE2 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 PGE2 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 PGE2 significantly increased C-fiber activities, but not Aδ-fiber activities. The PGE2-induced increase in C-fiber activities was inhibited by pretreatment with CL.

Conclusions

The present results clearly demonstrate that the β3-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 β3-AR agonist can inhibit PGE2-induced C-fiber hyperactivity. Neurourol. Urodynam. 29:771–776, 2010. © 2010 Wiley-Liss, Inc.

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