Existence of a beta 3-adrenoceptor and its functional role in the human ureter

Purpose: We tried to determine the beta-adrenoceptor (AR) subtypes distribu ted in the human ureter and to clarify their functional role in ureteral re laxation. Materials and Methods: 1) Effects of beta-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by beta -AR antagonists on isoprenaline (a non-selective beta-AR agonist)-induced e ffects were evaluated in vitro. 2) Displacement by beta-AR antagonists of [ H-3]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymeras e chain reaction assay was performed to determine the expression of the mRN A for beta 1-, beta 2- and beta 3-ARs in human ureteral smooth muscle. Results: 1) Isoprenaline and procaterol (a beta 2-AR agonist) concentration -dependently suppressed both spontaneous and KCl-induced contractions of th e human ureter, The beta 3-AR agonists, CGP-12177A and CL-316243, also supp ressed these ureteral contractions, but dobutamine (a beta 1-AR agonist) ha d little relaxing effect. The rank order of relaxing potency for the catech olamines was isoprenaline > adrenaline > noradrenaline. ICI-118,551 (a beta 2-AR antagonist) only partially antagonized the isoprenaline-induced relax ation. 2) Propranolol (a non-selective beta-AR antagonist) and ICI-118,551 concentration-dependently displaced [H-3] -dihydroalprenolol binding to the membrane with Ki values of 1.5 x 10(-9) M and 6.3 x 10(-9) M, respectively , while metoprolol (a beta 1-AR antagonist) was less effective in this assa y. 3) beta 1-, beta 2- and beta 3-AR mRNAs were all expressed in human uret eral smooth muscle. Conclusion: The present results provide the first evidence that the beta 3- AR subtype is distributed in human ureteral smooth muscle and that it, and beta 2-AR, mediate the ureteral relaxation induced by adrenergic stimulatio n.