The β3-adrenoceptor mediates the inhibitory effects of β-adrenoceptor agonists via the urothelium in pig bladder dome.
OBJECTIVE
Relaxation of detrusor muscle via β-adrenoceptors may contribute to urine storage during bladder filling. Thus there is increasing interest in β-adrenoceptor agonists as a potential treatment for detrusor overactivity. The role of the urothelium in bladder responses to β-adrenoceptor agonists is not yet clear, although we have shown that these agonists have a greater inhibitory effect on detrusor contraction when the urothelium is intact. The aim was to determine which β-adrenoceptor subtype is involved in this effect.


METHODS
Paired strips of pig bladder dome mucosa-intact and mucosa-denuded, were mounted in tissue baths. Relaxation responses were obtained to β-adrenoceptor agonists (isoprenaline, dobutamine, salbutamol or BRL37344) in carbachol pre-contracted tissues. Inhibitory effects were studied by obtaining concentration-response curves (CRCs) to carbachol in the presence and absence of β-adrenoceptor agonists. The inhibitory effects of isoprenaline were also studied following incubation with β-adrenoceptor antagonists (propranolol, CGP20712, ICI-118, 551 or SR 59230A; non selected, β(1), β(2) and β(3) selective respectively).


RESULTS
isoprenaline, dobutamine, salbutamol and BRL37344 all relaxed carbachol pre-contracted tissues and responses were similar in intact and denuded strips. In inhibition experiments, β-adrenoceptor agonists caused rightward shifts of carbachol CRCs. In intact strips the shift was greater with isoprenaline and BRL37344, but not with dobutamine or salbutamol. This increased shift was still observed in tissues pre-incubated with propranolo, CGP20712 and ICI-118, 551, but not with SR 59230A.


CONCLUSIONS
β(3)-adrenoceptors are involved in mediating inhibitory effects of β-adrenoceptor agonists on detrusor contractions via the urothelium in pig bladder dome.
Biomedical Research Centre, Sheffield Hallam University, Sheffield, UK.
Koichi
K
Masunaga
Christopher R
CR
Chapple
Neil G
NG
McKay
Masaki
M
Yoshida
Donna J
DJ
Sellers
D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology; D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism
D058665:Adrenergic beta-1 Receptor Agonists; D058666:Adrenergic beta-2 Receptor Agonists; D058667:Adrenergic beta-3 Receptor Agonists; D000319:Adrenergic beta-Antagonists; D018679:Cholinergic Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3