Expression and functional role of β3 -adrenoceptors in the human ureter.
OBJECTIVE
To investigate the presence of β-adrenoceptor subtypes in the human ureter, and to examine whether β(3) -adrenoceptors modulate relaxation of the human ureter.


METHODS
Expression of messenger ribonucleic acid of β-adrenoceptors in the human ureter was determined by reverse transcription polymerase chain reaction, and distribution of β-adrenoceptors was examined by immunohistochemistry. In functional studies, the relaxant effects of isoproterenol, procaterol, TRK-380, salbutamol and BRL 37344 on KCl-induced contraction of the human ureter were evaluated, and the inhibitory effects of isoproterenol, procaterol and TRK-380 on electrical field stimulation-induced contractions were determined.


RESULTS
Expression of β(1) -, β(2) - and β(3) -adrenoceptor messenger ribonucleic acid in the human ureter was confirmed by reverse transcription polymerase chain reaction. Positive staining for β(1) -, β(2) - and β(3) -adrenoceptor was identified not only in smooth muscle, but also in the urothelium of the human ureter. All β-adrenoceptor agonists decreased the tone of KCl-induced contractions of the human ureter with a rank order of relaxant effects of isoproterenol > procaterol > TRK-380 > salbutamol > BRL 37344. Furthermore, isoproterenol, procaterol and TRK-380 significantly decreased the amplitude of electrical field stimulation-induced contractions with a rank order of inhibitory effects of isoproterenol > procaterol > TRK-380.


CONCLUSIONS
Human ureteral relaxation is mediated by both β(2) - and β(3) -adrenoceptor stimulation. β(3) -Adrenoceptor agonists have the potential to relax the human ureter, and their clinical application in the treatment of ureteral stones is expected.
Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Rikiya
R
Matsumoto
Atsushi
A
Otsuka
Takahisa
T
Suzuki
Hitoshi
H
Shinbo
Takuji
T
Mizuno
Yutaka
Y
Kurita
Soichi
S
Mugiya
Seiichiro
S
Ozono
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D000420:Albuterol / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D017265:Procaterol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014513:Ureter / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019459:Urothelium / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
C547787:ADRB1 protein, human; C553443:ADRB2 protein, human; C568534:ADRB3 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004983:Ethanolamines; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344; D007545:Isoproterenol; D000420:Albuterol; D017265:Procaterol
TRK-380; human ureter; immunohistochemistry; reverse transcription polymerase chain reaction; β3-adrenoceptor agonist