Species differences in the distribution of beta-adrenoceptor subtypes in bladder smooth muscle

Br J Pharmacol. 1998 Jun;124(3):593-9. doi: 10.1038/sj.bjp.0701870.

Abstract

1. The beta-adrenoceptor (beta-AR) subtypes mediating relaxation of the rabbit, rat and canine detrusors were subjected to functional investigation using selective beta-AR agonists and antagonists. 2. In all three species, isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the detrusor. The rank order for their relaxing potency was isoprenaline>adrenaline>noradrenaline in rabbits and rats, but isoprenaline>noradrenaline>adrenaline in dogs. 3. Dobutamine did not produce relaxation of the detrusors at concentrations that are selective for beta1-AR. The selective beta2-AR agonist, procaterol, had a more potent relaxing effect on rabbit and rat detrusors than on the canine detrusor. CGP-12177A, a selective beta3-AR agonist, was more effective in the rabbit than in the other two species. On the other hand, the relaxing effect of another beta3-AR agonist, CL316243, was more pronounced in dogs and rats than in rabbits. 4. CGP-20712A (10(-9) to 10(-7) M), a selective beta1-AR antagonist, caused a slight rightward shift of the concentration-relaxation response curve for isoprenaline in the canine detrusor (pA2 9.41), but not in the rabbit and rat detrusors. ICI-118,551, a selective beta2-AR antagonist, antagonized the isoprenaline-induced relaxation in rabbits (pA2 9.45) and rats (pA2 9.05), but not in dogs. Bupranolol, a non-selective beta-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in the rabbit (pA2 9.32) and rat (pA2 8.98). However, higher concentrations (3 x 10(-8) to 10(-5) M) were needed to induce a rightward shift of the curve for isoprenaline in the dog (pA2 8.19) than in the other two species. 5. We have confirmed that the distribution of beta-AR subtypes in the detrusor muscle varies significantly from species to species and we provide here the first evidence of the presence of beta3-AR in the detrusor. It is suggested that the relaxation induced by adrenoceptor agonists in urinary bladder smooth muscle may be mediated mainly via beta2-AR in rabbits, via both beta2- and beta3-AR in rats, but mainly via beta3-AR in dogs.

Publication types

  • Comparative Study

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Dogs
  • Epinephrine / pharmacology
  • Female
  • In Vitro Techniques
  • Isoproterenol / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / metabolism*
  • Norepinephrine / pharmacology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Adrenergic, beta / metabolism*
  • Species Specificity
  • Urinary Bladder / metabolism*

Substances

  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Isoproterenol
  • Norepinephrine
  • Epinephrine