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Species differences in the distribution of β ‐adrenoceptor subtypes in bladder smooth muscle

1998; Wiley; Volume: 124; Issue: 3 Linguagem: Inglês

10.1038/sj.bjp.0701870

1476-5381

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

Hormonal and reproductive studies

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