OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Graham Johnson; Andrew Tabner; Apostolos Fakis; Rachelle Sherman; Victoria Chester; Elizabeth Bedford; Richard Jackson; Hari Ratan; Suzanne Mason Journal: Trials Date: 2022-04-25 Impact factor: 2.728
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