Effects of CL316,243, a beta 3-adrenoceptor agonist, and intravesical prostaglandin E2 on the primary bladder afferent activity of the rat.
OBJECTIVE
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 microg/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.
Aizawa
Naoki
N
Department of Urology, Faculty of Medicine, University Antwerp, Antwerp, Belgium.
Igawa
Yasuhiko
Y
Nishizawa
Osamu
O
Wyndaele
Jean-Jacques
JJ
D000283:Administration, Intravesical; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000344:Afferent Pathways / Q000187:drug effects; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology
D000318:Adrenergic beta-Agonists; D004149:Dioxoles; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D015232:Dinoprostone