Functional and molecular biological evidence for a possible β3-adrenoceptor in the human detrusor muscle
Functional and molecular biological evidence for a possible β3-adrenoceptor in the human detrusor muscle
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DOI：
10.1038/sj.bjp.0702358
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发表时间：
1999-02-01
影响因子：
7.3
通讯作者：
Andersson, KE
中科院分区：
文献类型：
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作者：
Igawa, Y;Yamazaki, Z;Andersson, KE
2异丙肾上腺素、去甲肾上腺素和肾上腺素分别对人逼尿肌产生浓度依赖性的松弛作用。它们的松弛效力的等级顺序是异丙肾上腺素(PD(2)6.37+/-0.07)大于或等于去甲肾上腺素(PD(2)6.07+/-0.12)大于或等于肾上腺素(PD(2)5.88+/-0.11)。3多巴酚丁胺(β(1)和β(2)-AR激动剂)和丙卡特罗(β(2)-AR激动剂)在10(-5)M BRL37344A、CL316243和CGP-12177A(β(3)-AR激动剂)的浓度下都不会产生任何明显的松弛，浓度高于10(-6)M时，BRL37344A、CL316243和CGP-12177A的POT值分别为6.42+/-0.25、5.53+/-0.09和5.74+/-0.14。4β(1)-AR拮抗剂CGP-20712A(10(-7)-10(-5)M)不影响异丙肾上腺素的松弛作用。而β(2)-AR拮抗剂ICI-118,551仅在最高浓度(10(-5)M)时使异丙肾上腺素的浓度-松弛曲线平行右移，其pK(B)值为5.71+/-0.19。此外，β(3)-AR拮抗剂SR58894A(10(-7)-10(-5)M)使异丙肾上腺素的浓度-松弛曲线右移，且呈浓度依赖关系。SChild曲线的pA(2)值和斜率分别为6.24+/-0.20和0.68+/-0.31.5逆转录-聚合酶链式反应显示，β(1)-、β(2)-和β(3)-AR的mRNAs在逼尿肌标本中均呈阳性表达。他们还表明，肾上腺素能刺激人逼尿肌所引起的松弛主要是通过激活β(3)-AR来实现的。
1 The possible existence of a beta(3)-adrenergic receptor (beta(3)-AR) in the human detrusor muscle was investigated by in vitro functional studies and analysis of mRNA expression.2 Isoprenaline, noradrenaline and adrenaline each produced a concentration-dependent relaxation of the human detrusor. The rank order for their relaxing potencies was isoprenaline (pD(2) 6.37 +/- 0.07) greater than or equal to noradrenaline (pD(2) 6.07 +/- 0.12) greater than or equal to adrenaline (pD(2) 5.88 +/- 0.11).3 Neither dobutamine (beta(1)- and beta(2)-AR agonist) nor procaterol (beta(2)-AR agonist) produced any significant relaxation at concentrations up to 10(-5) M. BRL37344A, CL316243 and CGP-12177A (beta(3)-AR agonists), relaxed the preparations significantly at concentrations higher than 10(-6) M. The pot values for BRL37344A, CL316243 and CGP-12177A were 6.42 +/- 0.25, 5.53 +/- 0.09 and 5.74 +/- 0.14, respectively.4 CGP-20712A (10(-7)-10(-5) M), a beta(1)-AR antagonist, did not affect the isoprenaline-induced relaxation. On the other hand, ICI-118,551, a beta(2)-AR antagonist, produced a rightward parallel shift of the concentration-relaxation curve for isoprenaline only at the highest concentration used (10(-5) M) and its pK(B) value was 5.71 +/- 0.19. Moreover, SR58894A (10(-7)-10(-5) M), a beta(3)-AR antagonist, caused a rightward shift of the concentration-relaxation curve for isoprenaline in a concentration-dependent manner. The pA(2) value and slope obtained from Schild plots were 6.24 +/- 0.20 and 0.68 +/- 0.31.5 The beta(1)-, beta(2)- and beta(3)-AR mRNAs were all positively expressed in detrusor smooth muscle preparations in a reverse transcription polymerase chain reaction assay.6 In conclusion, the present results provide the first evidence for the existence of the beta(3)-AR subtype in the human detrusor. They also suggest that the relaxation induced by adrenergic stimulation of the human detrusor is mediated mainly through beta(3)-AR activation.