Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?
Do β3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?
复制标题
DOI：
10.1152/ajprenal.00378.2011
复制
发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Petkov, Georgi V.
中科院分区：
文献类型：
--
作者：
Afeli, Serge A. Y.;Hristov, Kiril L.;Petkov, Georgi V.
Afeli SA，Hristov KL，Petkov GV.β 3肾上腺素能受体在豚鼠逼尿肌平滑肌兴奋性和收缩性中起作用吗？美国肾脏生理学杂志302：F251-F263，2012年。首次发表于2011年10月12日; doi：10.1152/ajprenal.00378.2011.-在许多物种中，β 3-肾上腺素能受体（β 3-AR）已被报道在前列腺素诱导的逼尿肌平滑肌（DSM）松弛中发挥主要作用。然而，它们在豚鼠DSM中的作用仍然存在争议。本研究的目的是研究β 3-AR是否在豚鼠DSM中表达，并评估两种选择性β 3-AR激动剂BRL 37344和L-755，507如何调节豚鼠DSM兴奋性和收缩性。我们使用了一个综合的实验方法，包括RT-PCR，膜片钳电生理学，和等距DSM张力记录。在新鲜分离的豚鼠DSM单细胞中检测到β 3-AR mRNA信息。BRL 37344而非L-755，507以浓度依赖性方式导致DSM自发阶段性收缩振幅和频率轻微降低。在阿托品（1 μ M）的存在下，只有自发阶段性收缩频率被抑制BRL 37344在较高浓度。BRL 37344和L-755，507均以浓度依赖性方式显著降低DSM卡巴胆碱诱导的相位和强直性收缩。然而，只有BRL 37344的抑制作用被β 3-AR拮抗剂SR 59230 A（10 μ M）部分拮抗。在阿托品存在下，BRL 37344和L-755，507对电场刺激引起的收缩没有抑制作用。膜片钳实验表明，BRL 37344（100 μ M）不影响DSM细胞静息膜电位和K+电导。虽然β 3-AR在mRNA水平表达，但它们在豚鼠DSM自发收缩性中起次要作用或不起作用，而不影响细胞兴奋性。然而，BRL 37344和L-755，507对豚鼠DSM卡巴胆碱诱导的收缩具有显著的抑制作用。这项研究概述了重要的DSM β 3-AR物种差异。
Afeli SA, Hristov KL, Petkov GV. Do beta 3-adrenergic receptors play a role in guinea pig detrusor smooth muscle excitability and contractility?. Am J Physiol Renal Physiol 302: F251-F263, 2012. First published October 12, 2011; doi:10.1152/ajprenal.00378.2011.-In many species, beta 3-adrenergic receptors (beta 3-ARs) have been reported to play a primary role in pharmacologically induced detrusor smooth muscle (DSM) relaxation. However, their role in guinea pig DSM remains controversial. The aim of this study was to investigate whether beta 3-ARs are expressed in guinea pig DSM and to evaluate how BRL37344 and L-755,507, two selective beta 3-AR agonists, modulate guinea pig DSM excitability and contractility. We used a combined experimental approach including RT-PCR, patch-clamp electrophysiology, and isometric DSM tension recordings. beta 3-AR mRNA message was detected in freshly isolated guinea pig DSM single cells. BRL37344 but not L-755,507 caused a slight decrease in DSM spontaneous phasic contraction amplitude and frequency in a concentration-dependent manner. In the presence of atropine (1 mu M), only the spontaneous phasic contractions frequency was inhibited by BRL37344 at higher concentrations. Both BRL37344 and L-755,507 significantly decreased DSM carbachol-induced phasic and tonic contractions in a concentration-dependent manner. However, only BRL37344 inhibitory effect was partially antagonized by SR59230A (10 mu M), a beta 3-AR antagonist. In the presence of atropine, BRL37344 and L-755,507 had no inhibitory effect on electrical field stimulation-induced contractions. Patch-clamp experiments showed that BRL37344 (100 mu M) did not affect the DSM cell resting membrane potential and K+ conductance. Although beta 3-ARs are expressed at the mRNA level, they play a minor to no role in guinea pig DSM spontaneous contractility without affecting cell excitability. However, BRL37344 and L-755,507 have pronounced inhibitory effects on guinea pig DSM carbachol-induced contractions. The study outlines important DSM beta 3-ARs species differences.