RT Journal Article
SR Electronic
T1 Role of the β<sub>3</sub>-Adrenoceptor in Urine Storage in the Rat: Comparison between the Selective β<sub>3</sub>-Adrenoceptor Agonist, CL316,243, and Various Smooth Muscle Relaxants
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 939
OP 945
VO 293
IS 3
A1 Hiroo Takeda
A1 Yoshinobu Yamazaki
A1 Masuo Akahane
A1 Yasuhiko Igawa
A1 Yukiyoshi Ajisawa
A1 Osamu Nishizawa
YR 2000
UL http://jpet.aspetjournals.org/content/293/3/939.abstract
AB The objective of this study was to compare the effects of a β3-adrenoceptor (β3-AR) agonist on bladder function and cardiovascular parameters in rats with those of several drugs that act on smooth muscle. CL316,243 (β3-AR agonist), isoproterenol (nonselective β-AR agonist), procaterol (β2-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 β-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 β3-AR stimulation, we conclude that this β3-AR agonist may have potential in pollakiuria (frequent urination) as a therapeutic agent without cardiovascular side effects. The American Society for Pharmacology and Experimental Therapeutics