Non-genomic mechanism of 17 beta-oestradiol-induced inhibition of contraction in mammalian vascular smooth muscle
Non-genomic mechanism of 17 beta-oestradiol-induced inhibition of contraction in mammalian vascular smooth muscle
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DOI：
10.1113/jphysiol.1997.sp021944
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发表时间：
1997-03-01
影响因子：
5.5
通讯作者：
Gaznabi, AKM
中科院分区：
文献类型：
--
作者：
Kitazawa, T;Hamada, E;Gaznabi, AKM
1. 0.1-10μM的17β-雌二醇(E2)直接抑制各种强直性和阶段性平滑肌收缩。采用完整、透化的平滑肌条带和分离的单细胞研究了雌激素诱导的收缩抑制机制。 2．在内皮剥脱的血管平滑肌中，E2 减弱高力诱导的力量发展和肌球蛋白轻链磷酸化，并产生快速且可逆的松弛。这些抑制作用在组织类型（股动脉与门静脉）、物种（大鼠与兔）或性别之间没有显着差异。3．对几种甾体和非甾体雌激素类似物的抑制效力进行了检查，它们的作用大部分是立体特异性的。然而，两种与核雌激素受体亲和力可忽略不计的类固醇也强烈抑制高K+诱导的收缩。4．包括蛋白质合成抑制剂、RNA合成抑制剂和雌激素受体拮抗剂在内的基因组调节剂不影响E2的抑制作用。环核苷酸依赖性蛋白激酶抑制剂不降低E2效应。5．激动剂和肌醇 1,4,5-三磷酸 (IP3) 从细胞内储存的 Ca2+ 释放似乎不受 E2 调节。兰尼碱和毒胡萝卜素预处理均不影响EB诱导的高K+诱导收缩的抑制作用。6． E2 对调节和收缩装置的正常或 GTP gamma S 增加的 Ca2+ 敏感性没有影响。7． E2 及其类似物快速抑制离体平滑肌细胞中电压依赖性 L 型 Ca2+ 通道电流。 E2诱导的电流抑制不需要重复刺激。8．这项研究强烈表明，在药理学浓度下，雌激素主要通过以非基因组方式抑制 L 型 Ca2+ 通道来减少 Ca2+ 流入，并减少肌球蛋白轻链磷酸化和平滑肌收缩。
1. 17 beta-Oestradiol (E2) at 0.1-10 mu M directly inhibited various tonic and phasic smooth muscle contractions. The mechanism(s) of oestrogen-induced inhibition of contraction was studied using intact and permeabilized strips and isolated single cells of smooth muscle.2. In endothelium-denuded vascular smooth muscle, E2 attenuated high lif-induced force development and myosin light chain phosphorylation, and produced rapid and reversible relaxation. There were no significant differences in these inhibitory effects between tissue types (femoral artery vs. portal vein), species (rat vs. rabbit) or sexes.3. The inhibitory potencies of several steroidal and non-steroidal oestrogen analogues were examined and their effects were for the most part stereo-specific. However, two steroids with negligible affinities for the nuclear oestrogen receptor also strongly inhibited high K+-induced contraction.4. Genomic modulators including a protein synthesis inhibitor, an RNA synthesis inhibitor, and oestrogen receptor antagonists did not affect the inhibitory actions of E2. Inhibitors of cyclic nucleotide-dependent protein kinases did not reduce the E2 effect.5. Ca2+ release from intracellular stores by agonists and by inositol 1,4,5-trisphosphate (IP3) does not appear to be modulated by E2. Neither pretreatment with ryanodine nor with thapsigargin affected the EB-induced inhibition of high K+-induced contraction.6. E2 had no effect on either normal or GTP gamma S-increased Ca2+ sensitivity of the regulatory and contractile apparatus.7. E2 and its analogues rapidly inhibited voltage-dependent L-type Ca2+ channel currents in isolated smooth muscle cells. Repetitive stimulation was not required for E2-induced inhibition of the currents.8. This study strongly suggests that at pharmacological concentrations oestrogen primarily reduces Ca2+ influx through inhibition of L-type Ca2+ channels in a non-genomic manner and decreases myosin light chain phosphorylation and contraction of smooth muscle.