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

Abstract

1 The b-adrenoceptor (b-AR) subtypes mediating relaxation of the rabbit, rat and canine detrusors were subjected to functional investigation using selective b-AR agonists and antagonists. 2 In all three species, isoprenaline, noradrenaline and adrenaline each produced a concentrationdependent relaxation of the detrusor. The rank order for their relaxing potency was isoprenaline4 adrenaline4noradrenaline in rabbits and rats, but isoprenaline4noradrenaline4adrenaline in dogs. 3 Dobutamine did not produce relaxation of the detrusors at concentrations that are selective for b 1 -AR. The selective b 2 -AR agonist, procaterol, had a more potent relaxing e ect on rabbit and rat detrusors than on the canine detrusor. CGP-12177A, a selective b 3 -AR agonist, was more e ective in the rabbit than in the other two species. On the other hand, the relaxing e ect of another b 3 -AR agonist, CL316243, was more pronounced in dogs and rats than in rabbits. 4 CGP-20712A (10 79 to 10 77 M), a selective b 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 b 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 b-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 (3610 78 to 10 75 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. 5. We have con®rmed that the distribution of b-AR subtypes in the detrusor muscle varies signi®cantly from species to species and we provide here the ®rst evidence of the presence of b 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 b 2 -AR in rabbits, via both b 2 -and b 3 -AR in rats, but mainly via b 3 -AR in dogs.

Does Cyclic AMP Mediate Rat Urinary Bladder Relaxation by Isoproterenol?

“…Thus, measurements in the presence of KCl yielded approximately one log unit lower isoproterenol potency but somewhat greater maximum effects. This is in line with indirect comparisons in the published literature, where Table 1. an pEC 50 for isoproterenol of 8.3 (Yamazaki et al, 1998) versus 7.2 (Longhurst andLevendusky, 1999) and of 9.1 (Yamazaki et al, 1998) versus 7.3 (Oshita et al, 1997 were reported in rats and rabbits, respectively, for passive tension versus precontraction. Physiological urinary potassium concentrations range between 1 and 50 mM, but due to the presence of the urothelium, it is not fully clear whether and/or how much of this variation is sensed by bladder smooth muscle cells.…”

“…Previous studies have employed two different approaches to measure urinary bladder relaxation by ␤-adrenergic receptor agonists, i.e., relaxation against passive tension (Lecci et al, 1998;Yamazaki et al, 1998;Igawa et al, 1999) or relaxation against active tone, induced, e.g., by depolarizing concentrations of KCl (Oshita et al, 1997;Longhurst and Levendusky, 1999;Kobayashi et al, 2000;Yamanishi et al, 2002Yamanishi et al, , 2003. Since we hypothesized that the extracellular potassium concentration may affect the relative role of potassium channels, we have used both approaches in parallel.…”

“…Since previous studies have failed to unequivocally identify the ␤-adrenergic receptor subtype mediating bladder relaxation in the rat, we have based our present study on isoproterenol, an agonist that similarly acts on all known ␤-adrenergic receptor subtypes (Hoffmann et al, 2004). Previous studies on bladder relaxation by ␤-adrenergic agonists have employed two different approaches: relaxation against passive tension (Lecci et al, 1998;Yamazaki et al, 1998;Igawa et al, 1999) or relaxation against active tone, induced, e.g., by depolarizing concentrations of KCl (Oshita et al, 1997;Longhurst and Levendusky, 1999;Kobayashi et al, 2000;Yamanishi et al, 2002). Since we expected this methodological difference to affect the relative role of potassium channels in bladder relaxation, all our experiments were performed under both conditions.…”

Characterization of β-Adrenoceptor Subtype in Bladder Smooth Muscle in Cynomolgus Monkey

“…It is therefore concluded that the relaxation of the monkey detrusor is mediated almost entirely via the b3-adrenoceptor. There are many reports of b3-adrenoceptors coexisting with other subtypes of badrenoceptors in urinary bladders: for example, b1-and b3-adrenoceptors in dog (12), b2-and b3-adrenoceptors in rat (12), and b 3-and an atypical b -adrenoceptor in both ferret (13) and human (5). So far, the monkey is the only instance of detrusor relaxation being mediated by the b3-adrenoceptor alone (although we cannot entirely exclude a very small contribution by another subtype).…”

GW427353 (Solabegron), a Novel, Selective β3-Adrenergic Receptor Agonist, Evokes Bladder Relaxation and Increases Micturition Reflex Threshold in the Dog

“…Evidence suggests that species differences exist in the distributions and roles of ␤-ARs in the bladder (for comprehensive review, see Michel and Vrydag, 2006). Bladder relaxation evoked by ␤-AR agonists is mediated mainly via ␤ 1 -ARs in cats (Nergardh et al, 1977) and guinea pigs (Li et al, 1992), by ␤ 2 -ARs in rabbits, by both ␤ 2 -and ␤ 3 -ARs in rats (Yamazaki et al, 1998) and pigs (Yamanishi et al, 2002), and by ␤ 3 -ARs in the ferrets (Takeda et al, 2000), dogs (Yamazaki et al, 1998), and primates (Takeda et al, 2002a). Based on mRNA expression, at least 95% of the adrenoceptor message in human bladder comprises the ␤ 3 -AR subtype (Nomiya and Yamaguchi, 2003).…”