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

Abstract

Abbreviations & AcronymsObjectives: To investigate the presence of b-adrenoceptor subtypes in the human ureter, and to examine whether b3-adrenoceptors modulate relaxation of the human ureter. Methods: Expression of messenger ribonucleic acid of b-adrenoceptors in the human ureter was determined by reverse transcription polymerase chain reaction, and distribution of b-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 stimulationinduced contractions were determined. Results: Expression of b1-, b2-and b3-adrenoceptor messenger ribonucleic acid in the human ureter was confirmed by reverse transcription polymerase chain reaction. Positive staining for b1-, b2-and b3-adrenoceptor was identified not only in smooth muscle, but also in the urothelium of the human ureter. All b-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 b2-and b3-adrenoceptor stimulation. b3-Adrenoceptor agonists have the potential to relax the human ureter, and their clinical application in the treatment of ureteral stones is expected.

Editorial Comment from Dr Michel to Expression and functional role of β3‐adrenoceptors in the human ureter

“…A previous study has reported the presence of mRNA for all three β‐adrenoceptor subtypes in the human ureter, and showed relaxation against passive tension by β 2 ‐ and β 3 ‐, but not by β 1 ‐adrenoceptor agonists; as a β 2 ‐selective antagonist showed only poor inhibition of relaxation, a major functional role of β 3 ‐adrenoceptors was implied . The present study confirms the previously reported mRNA data, and expands them to the protein level using immunohistochemistry in both smooth muscle and urothelium; in analogy to bladder findings, this raises the possibility that β 3 ‐adrenoceptor agonists in the ureter might also in part act indirectly on muscle tone by primarily affecting urothelial function. The present study also extends the previous functional findings by showing relaxation against KCl‐ and field stimulation‐induced tone.…”

“…In this issue of the Journal, Matsumoto et al . report on the expression and function of β 3 ‐adrenoceptors in the human ureter . They propose that ureteral β 3 ‐adrenoceptors might be a target for medical stone expulsion therapy.…”

“…In this issue of the Journal, Matsumoto et al report on the expression and function of b3-adrenoceptors in the human ureter. 6 They propose that ureteral b3-adrenoceptors might be a target for medical stone expulsion therapy. The sympathetic nervous system contributes to the regulation of ureteral tone through both a1and b-adrenoceptors, mediating smooth muscle contraction and relaxation, respectively.…”

Rat β3-adrenoceptor protein expression: antibody validation and distribution in rat gastrointestinal and urogenital tissues

“…While we are not aware of β 3 -adrenoceptor mRNA studies on rat or mouse ureter, its expression level in human ureter was reported to be low (Park et al 2000;Matsumoto et al 2013); moreover, in some species including humans, ureter relaxation by β 3 -adrenoceptor agonists has been reported (Park et al 2000;Matsumoto et al 2013). Several studies have reported β 3 -adrenoceptor mRNA in rat bladder, including specifically in its urothelium (Seguchi et al 1998;Fujimura et al 1999;Barendrecht et al 2009;Kullmann et al 2011).…”

Editorial Comment from Dr Füllhase to Expression and functional role of β3‐adrenoceptors in the human ureter

“…As the authors of the presented manuscript state, the effects of some β 3 agonists on ureteral tone have already been investigated. However, the presented study by Matsumoto et al . is remarkable, as it is the first one to report on the potential benefits of mirabegron, which is already approved for human use, on ureteral contractions, and hence its potential role in medical expulsive therapy (MET).…”