Smooth Muscle and Molecular Pharmacology Laboratory, Department of Pharmacology & Toxicology, College of Veterinary Science and Animal Husbandry, U.P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan (DUVASU), Mathura, 281001, India.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Aug;394(8):1651-1664. doi: 10.1007/s00210-021-02084-4. Epub 2021 Apr 22.
This study unravels the differential involvement of calcium signaling pathway(s) in PGF-induced contractions in myometrium of nonpregnant (NP) and pregnant buffaloes. Compared to the myometrium of pregnant animals, myometrium of NP buffaloes was more sensitive to PGF as manifested by changes in mean integral tension (MIT) and tonicity. In the presence of nifedipine, myometrial contraction to PGF was significantly attenuated in both NP and pregnant uteri; however, mibefradil and NNC 55-0396 produced inhibitory effects only in uterus of pregnant animals, thus suggesting the role of extracellular Ca influx through nifedipine-sensitive L-type Ca-channels both in NP and pregnant, but T-type Ca channels seem to play a role only during pregnancy. Entry of extracellular Ca is triggered by enhanced functional involvement of Pyr3-sensitive TRPC3 channels and Rho-kinase pathways as evidenced by a significant rightward shift of the concentration-response curve of PGF in the presence of Pyr3 and Y-27632 in NP myometrium. But significant down-expressions of TRPC3 and Rho-A proteins during pregnancy apparently facilitate uterine quiescence. In the presence of Ca-free solution and cyclopiazonic acid (SERCA blocker), feeble contraction to PGF was observed in both NP and pregnant myometrium which suggests minor role of intracellular source of Ca in mediating PGF-induced contractions in these tissues.
本研究揭示了钙信号通路在未怀孕（NP）和怀孕水牛的子宫肌中 PGF 诱导收缩中的差异参与。与怀孕动物的子宫肌相比，NP 水牛的子宫肌对 PGF 更为敏感，表现为平均积分张力（MIT）和紧张度的变化。在硝苯地平存在的情况下，PGF 引起的子宫肌收缩在 NP 和怀孕子宫中均显著减弱；然而，米贝地尔和 NNC 55-0396 仅在怀孕动物的子宫中产生抑制作用，因此表明细胞外 Ca 流入通过硝苯地平敏感的 L 型 Ca 通道在 NP 和怀孕中都起作用，但 T 型 Ca 通道似乎仅在怀孕期间起作用。细胞外 Ca 的进入是由 Pyr3 敏感的 TRPC3 通道和 Rho-激酶途径的功能增强触发的，这可以通过在 NP 子宫肌中 Pyr3 和 Y-27632 的存在下 PGF 的浓度-反应曲线的显著右移来证明。但在怀孕期间 TRPC3 和 Rho-A 蛋白的明显下调显然促进了子宫静止。在无钙溶液和环匹阿尼酸（SERCA 阻断剂）存在的情况下，NP 和怀孕的子宫肌中均可观察到对 PGF 的微弱收缩，这表明细胞内 Ca 源在介导这些组织中 PGF 诱导的收缩中作用较小。
