Vol. 293, Issue 3, 939-945, June 2000

Role of the ₃-Adrenoceptor in Urine Storage in the Rat: Comparison between the Selective ₃-Adrenoceptor Agonist, CL316,243, and Various Smooth Muscle Relaxants¹

Hiroo Takeda, Yoshinobu Yamazaki, Masuo Akahane, Yasuhiko Igawa, Yukiyoshi Ajisawa and Osamu Nishizawa

Central Research Laboratory, Kissei Pharmaceutical Co., Ltd., Nagano (H.T., Y.Y., M.A., Y.A.); and Department of Urology, Shinshu University School of Medicine, Nagano, Japan (Y.I., O.N.)

The objective of this study was to compare the effects of a ₃-adrenoceptor (₃-AR) agonist on bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (₃-AR agonist), isoproterenol (nonselective -AR agonist), procaterol (₂-AR agonist), verapamil (Ca²⁺ antagonist), and papaverine (antispastic drug) each evoked a concentration-dependent relaxation of the detrusor in vitro. They also reduced bladder pressure in anesthetized rats, the -AR agonists apparently being more potent than the other drugs. Atropine (muscarinic antagonist) neither relaxed detrusor strips nor reduced bladder pressure. In anesthetized rats, CL316,243 and atropine each had only a slight influence on blood pressure and heart rate, but isoproterenol, procaterol, verapamil, and papaverine significantly affected cardiovascular function at the same dose range as that required to reduce bladder pressure. In cystometry experiments, CL316,243 (10 µg/kg i.v.), verapamil (1 mg/kg i.v.), and papaverine (1 mg/kg i.v.) all significantly prolonged micturition interval and increased bladder capacity, but did not change the residual urine volume after a micturition contraction. Procaterol (100 µg/kg i.v.) prolonged the micturition interval and increased both bladder capacity and residual urine volume (all significantly). Atropine (100 µg/kg i.v.) reduced micturition pressure and increased residual urine volume (both significantly). Because the human detrusor, like the rat detrusor, relaxes on ₃-AR stimulation, we conclude that this ₃-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects.