Kitazawa T, Hamada E, Kitazawa K, Gaznabi A K
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington DC 20007, USA.
J Physiol. 1997 Mar 1;499 ( Pt 2)(Pt 2):497-511. doi: 10.1113/jphysiol.1997.sp021944.
17 beta-Oestradiol (E2) at 0.1-10 microM 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 K(+)-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 E2-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.
17β-雌二醇（E2）在0.1 - 10微摩尔浓度时可直接抑制各种紧张性和阶段性平滑肌收缩。利用完整和通透的肌条以及分离的平滑肌单细胞，研究了雌激素诱导的收缩抑制机制。2. 在去内皮的血管平滑肌中，E2减弱了高钾（K⁺）诱导的力量产生和肌球蛋白轻链磷酸化，并产生快速且可逆的舒张。这些抑制作用在组织类型（股动脉与门静脉）、物种（大鼠与兔子）或性别之间没有显著差异。3. 检测了几种甾体和非甾体雌激素类似物的抑制效力，其作用大多具有立体特异性。然而，两种对核雌激素受体亲和力可忽略不计的甾体也强烈抑制高钾（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的作用效果。5. 激动剂和肌醇1,4,5 - 三磷酸（IP3）从细胞内储存释放Ca²⁺似乎不受E2调节。用兰尼碱或毒胡萝卜素预处理均不影响E2诱导的对高钾（K⁺）诱导收缩的抑制作用。6. E2对调节和收缩装置的正常或GTPγS增加的Ca²⁺敏感性均无影响。7. E2及其类似物可快速抑制分离的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. 本研究强烈表明，在药理浓度下，雌激素主要通过非基因组方式抑制L型Ca²⁺通道来减少Ca²⁺内流，并降低肌球蛋白轻链磷酸化和平滑肌收缩。
