Existence of a beta3-adrenoceptro and its functional role in the human ureter.
OBJECTIVE
We tried to determine the beta-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation.


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.


CONCLUSIONS
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.
Park
Y C
YC
Department of Urology, Kinki University School of Medicine, Osaka, and the Division of Discovery Research, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Tomiyama
Y
Y
Hayakawa
K
K
Akahane
M
M
Ajisawa
Y
Y
Miyatake
R
R
Kiwamoto
H
H
Sugiyama
T
T
Kurita
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017931:DNA Primers; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism* / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014513:Ureter / Q000378:metabolism / Q000502:physiology
D017931:DNA Primers; D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3