Sharma Abhishek, Nakade Udayraj P, Choudhury Soumen, Garg Satish Kumar
Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India.
Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, UP Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Gau Anusandhan Sansthan, Mathura, U.P. 281 001, India.
Theriogenology. 2017 Apr 1;92:176-189. doi: 10.1016/j.theriogenology.2016.12.008. Epub 2016 Dec 7.
Present study unravels the involvement of different calcium signaling pathways in oxytocin-induced contractions in myometrium of non-pregnant and pregnant buffaloes during early and mid-pregnancy stages. Uteri of pregnant animals were more sensitive than of non-pregnant buffaloes. Phasic contractions and frequency of contraction significantly increased with advancement of pregnancy, while tonic contractions non-significantly and amplitude significantly decreased from six months pregnancy onward. Oxytocin produced concentration-dependent-contraction on isolated myometrial strips of pregnant and non-pregnant buffaloes and the dose response curves (DRCs) of oxytocin were significantly (P < 0.05) shifted to right in the presence of nifedipine (1 μM), in Ca-free Ringer Locke solution (RLS), ruthenium red (30 μM), ruthenium red + nifedipine, cyclopiazonic acid (CPA; Ca free RLS as well as RLS), CPA (10 μM)+nifedipine, U-73122 (1 μM) + nifedipine and SKF96365 (25 μM) on uteri of non-pregnant and pregnant (early and mid) animals. The DRCs were also significantly shifted towards right in the presence of Y-27632 (10 μM), GF109203X (5 μM) and Pyr3 (10 μM) on uteri of non-pregnant and early pregnancy stage buffaloes while only in the presence of U-73122 (1 μM) on uteri of mid-pregnancy stage buffaloes. Our finding suggest that and L-type Ca channels, IP3-RyR-gated, and store-operated calcium channels including transient receptor potential channel (TRPC) pathways play significant role in mediating oxytocin-induced contractions in myometrium of pregnant and non-pregnant buffaloes. SERCA plays major role only during early-pregnancy while functional role of protein kinase C (PKC), Rho-kinase and TRPC3 pathways decreased and role of G-protein coupled receptor-phospholipase C (GPCR-PLC) pathway increased with advancement of pregnancy.
本研究揭示了不同钙信号通路在非妊娠和妊娠水牛子宫肌层中,于妊娠早期和中期阶段催产素诱导的收缩过程中的作用。妊娠动物的子宫比非妊娠水牛的子宫更敏感。随着妊娠进展,相性收缩和收缩频率显著增加,而强直性收缩无显著变化,且从妊娠六个月起收缩幅度显著降低。催产素对妊娠和非妊娠水牛的离体子宫肌条产生浓度依赖性收缩,在硝苯地平(1 μM)、无钙林格洛克溶液(RLS)、钌红(30 μM)、钌红 + 硝苯地平、环匹阿尼酸(CPA;无钙RLS以及RLS)、CPA(10 μM)+ 硝苯地平、U - 73122(1 μM)+ 硝苯地平以及SKF96365(25 μM)存在的情况下,催产素的剂量反应曲线(DRCs)在非妊娠和妊娠(早期和中期)动物的子宫上显著(P < 0.05)右移。在Y - 27632(10 μM)、GF109203X(5 μM)和Pyr3(10 μM)存在的情况下,DRCs在非妊娠和妊娠早期阶段水牛的子宫上也显著右移,而仅在U - 73122(1 μM)存在的情况下,在妊娠中期阶段水牛的子宫上DRCs右移。我们的研究结果表明,L型钙通道、IP3 - RyR门控通道以及包括瞬时受体电位通道(TRPC)途径在内的储存性钙通道在介导妊娠和非妊娠水牛子宫肌层中催产素诱导的收缩中起重要作用。肌浆网钙ATP酶(SERCA)仅在妊娠早期起主要作用,而蛋白激酶C(PKC)、 Rho激酶和TRPC3途径的功能作用随着妊娠进展而降低,G蛋白偶联受体 - 磷脂酶C(GPCR - PLC)途径的作用增加。