Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via β-adrenoceptors
Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via β-adrenoceptors
复制标题
DOI：
10.1016/j.ejphar.2005.06.029
复制
发表时间：
2005-08-22
影响因子：
5
通讯作者：
Yamaguchi, O
中科院分区：
文献类型：
--
作者：
Uchida, H;Shishido, K;Yamaguchi, O
我们研究了大鼠逼尿肌在有和没有预收缩的情况下，通过β -肾上腺素能受体的camp依赖性和非依赖性松弛机制。采用微透析技术测定同一逼尿肌组织的逼尿肌张力和cAMP水平。在非收缩组织中，异丙肾上腺素、瘦肉精（β(2)-肾上腺素能受体激动剂）和FR165101、((8S)-8-{[（2R)-2-（3-氯苯基）-2-羟乙基]氨基}-6,7,8,9-四氢- 5h -苯并环庚烯-2-基）氧]醋酸盐酸盐（β(3)-肾上腺素能受体激动剂）松弛的逼尿肌和cAMP水平也呈浓度依赖性增加。SQ22536（腺苷酸环化酶抑制剂）明显抑制松弛，提示β -肾上腺素受体介导的松弛可能主要归因于camp依赖机制。在高K+预收缩组织中，尽管松弛以浓度依赖的方式推进，但在浓度超过10(-7)m时，cAMP的产生达到平台。然而，大电导，Ca2+激活的K+ (BKCa)通道抑制剂，肉毒素和iberiotoxin明显抑制松弛。这些结果表明，除了camp依赖途径外，BKCa通道还参与了β -肾上腺素能受体激动剂诱导的预收缩逼尿肌松弛。(c) 2005 Elsevier B.V.版权所有
We investigated the cAMP-dependent and -independmt mechanisms of relaxation via beta-adrenoceptor in rat detrusor muscle with and without pre-contraction. A microdialysis technique was used to measure detrusor tension and cAMP level on the same detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta(2)-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl] amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta(3)-adrenoceptor agonist) relaxed detrusor muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BKCa) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BKCa channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted detrusor muscle. (c) 2005 Elsevier B.V. All rights reserved.