Expression and functional role of β3‐adrenoceptors in the human ureter

Objectives To investigate the presence of β-adrenoceptor subtypes in the human ureter, and to examine whether β3-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 β1-, β2- and β3-adrenoceptor messenger ribonucleic acid in the human ureter was confirmed by reverse transcription polymerase chain reaction. Positive staining for β1-, β2- and β3-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 β2- and β3-adrenoceptor stimulation. β3-Adrenoceptor agonists have the potential to relax the human ureter, and their clinical application in the treatment of ureteral stones is expected.