Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors

Eur J Pharmacol. 2005 Aug 22;518(2-3):195-202. doi: 10.1016/j.ejphar.2005.06.029.


We investigated the cAMP-dependent and -independent mechanisms of relaxation via beta-adrenoceptor in rat detrusor muscle with and without pre-contraction. A microdialysis technique was used to measure detrusor tension and cAMP level on the same detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta2-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta3-adrenoceptor agonist) relaxed detrusor muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BK(Ca)) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BK(Ca) channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted detrusor muscle.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / pharmacology
  • Adenylyl Cyclase Inhibitors
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Benzocycloheptenes / pharmacology
  • Clenbuterol / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP / physiology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Microdialysis
  • Muscle Relaxation / drug effects
  • Muscle Relaxation / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Peptides / pharmacology
  • Potassium Channel Blockers / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / physiology*
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiology*


  • Adenylyl Cyclase Inhibitors
  • Adrenergic beta-Agonists
  • Benzocycloheptenes
  • Enzyme Inhibitors
  • FK 175
  • Peptides
  • Potassium Channel Blockers
  • Receptors, Adrenergic, beta
  • 9-(tetrahydro-2-furyl)-adenine
  • iberiotoxin
  • Cyclic AMP
  • Adenine
  • Isoproterenol
  • Clenbuterol