EXISTENCE OF A β3-ADRENOCEPTOR AND ITS FUNCTIONAL ROLE IN THE HUMAN URETER

PURPOSE: We tried to determine the beta-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation. 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 effects were evaluated in vitro. 2) Displacement by beta-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for beta1-, beta2- and beta3-ARs in human ureteral smooth muscle. RESULTS: 1) Isoprenaline and procaterol (a beta2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The beta3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a beta1-AR agonist) had little relaxing effect. The rank order of relaxing potency for the catecholamines was isoprenaline > adrenaline > noradrenaline. ICI-118,551 (a beta2-AR antagonist) only partially antagonized the isoprenaline-induced relaxation. 2) Propranolol (a non-selective beta-AR antagonist) and ICI-118,551 concentration-dependently displaced [3H]-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 beta1-AR antagonist) was less effective in this assay. 3) beta1-, beta2- and beta3-AR mRNAs were all expressed in human ureteral smooth muscle. CONCLUSION: The present results provide the first evidence that the beta3-AR subtype is distributed in human ureteral smooth muscle and that it, and beta2-AR, mediate the ureteral relaxation induced by adrenergic stimulation.