Functional characterization of beta-adrenoceptor subtypes in the canine and rat lower urinary tract.
OBJECTIVE
We compared the effect of a beta 3-adrenoceptor (AR) agonist with that of beta 1 and beta 2-AR agonists on the urethra and bladder in the dog and rat.


METHODS
In an in vitro experiment we studied the relaxant effect of subtype selective beta-AR agonists in canine and rat urethral and bladder smooth muscle using an organ bath method. In addition, in urethane anesthetized rats we measured urethral pressure and bladder pressure simultaneously in the presence of the beta 3-agonist CL316243 and the beta 2-agonist procaterol in 4 or 5 animals.


RESULTS
In the dog the relaxing effects of isoprenaline in the distal urethra were about half those seen in the detrusor and trigone. The rank order of relaxing potency was CL316243 > dobutamine (beta 1-agonist) = procaterol in detrusor and trigone but procaterol > dobutamine = CL316243 in the prostatic and distal urethra. In rat urethral smooth muscle in vitro the corresponding order was procaterol > CL316243 > dobutamine and the maximal relaxation to each agonist was about half that seen in the bladder. In the anesthetized rat procaterol clearly decreased urethral pressure but CL316243 produced only a slight decrease at its maximal dose, although each agonists clearly reduced bladder pressure. The beta 2-antagonist ICI-118551 counteracted the decrease in urethral and bladder pressure induced by procaterol.


CONCLUSIONS
In rats and dogs a selective beta 3-AR agonist can decrease bladder pressure without affecting urethral pressure.
Takeda
Hiroo
H
Division of Discovery Research, Kissei Pharmaceutical Co., Ltd., Hotaka, Nagano-Prefecture, Japan.
Matsuzawa
Akane
A
Igawa
Yasuhiko
Y
Yamazaki
Yoshinobu
Y
Kaidoh
Kouich
K
Akahane
Satoshi
S
Kojima
Masami
M
Miyata
Hirsohi
H
Akahane
Masuo
M
Nishizawa
Osamu
O
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004149:Dioxoles / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D017265:Procaterol / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D014521:Urethra / Q000378:metabolism / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004149:Dioxoles; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D004280:Dobutamine; C026777:ICI 118551; D007545:Isoproterenol; D017265:Procaterol