Seguchi H, Nishimura J, Zhou Y, Niiro N, Kumazawa J, Kanaide H
Division of Molecular Cardiology, Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Urol. 1998 Jun;159(6):2197-201. doi: 10.1016/S0022-5347(01)63305-6.
To investigate the expression of beta-adrenoceptor (AR) subtypes responsible for detrusor smooth muscle relaxation.
Isolated rat detrusor smooth muscle was examined by tension measurement and reverse transcription polymerase chain reaction (RT-PCR).
Norepinephrine (NE), epinephrine (EP) and isoproterenol (ISO) were found to relax the detrusor muscle pre-contracted by 6 x 10(-7) M carbachol in the presence of 10(-6) M phentolamine. NE relaxed the detrusor muscle as potently as EP. This potency order (NE=EP) thus indicated the beta-ARs of the rat detrusor muscle to possibly be a beta1 subtype. However, in the presence of 10(-6) M propranolol, beta1- and beta2- but not beta3-AR antagonist, NE showed a more potent relaxation than EP. This observation indicated that the rat detrusor muscle also possesses beta3-AR. RT-PCR revealed all three subtypes of beta-AR mRNA, namely beta1-, beta2- and beta3-AR mRNA, to be expressed in rat detrusor smooth muscle cells.
We concluded that beta3-ARs exist in rat detrusor smooth muscle based on both pharmacological and molecular biological studies. Based on these findings, beta-ARs of rat detrusor smooth muscle are considered to be mixed populations consisting of three subtypes which play an important role in relaxing smooth muscle in response to catecholamines.
研究负责逼尿肌平滑肌舒张的β-肾上腺素能受体(AR)亚型的表达。
通过张力测量和逆转录聚合酶链反应(RT-PCR)对分离的大鼠逼尿肌平滑肌进行检测。
在存在10⁻⁶ M酚妥拉明的情况下,发现去甲肾上腺素(NE)、肾上腺素(EP)和异丙肾上腺素(ISO)可使由6×10⁻⁷ M卡巴胆碱预收缩的逼尿肌舒张。NE使逼尿肌舒张的效力与EP相当。这种效力顺序(NE = EP)因此表明大鼠逼尿肌的β-AR可能是β1亚型。然而,在存在10⁻⁶ M普萘洛尔(β1和β2而非β3-AR拮抗剂)的情况下,NE显示出比EP更强的舒张作用。这一观察结果表明大鼠逼尿肌也具有β3-AR。RT-PCR显示β-AR mRNA的所有三种亚型,即β1-、β2-和β3-AR mRNA,在大鼠逼尿肌平滑肌细胞中均有表达。
基于药理学和分子生物学研究,我们得出结论,β3-AR存在于大鼠逼尿肌平滑肌中。基于这些发现,大鼠逼尿肌平滑肌的β-AR被认为是由三种亚型组成的混合群体,它们在响应儿茶酚胺时对平滑肌舒张起重要作用。