Calcium Channels, Rho-Kinase, Protein Kinase-C, and Phospholipase-C Pathways Mediate Mercury Chloride-Induced Myometrial Contractions in Rats
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Adverse effects of mercury on female reproduction are reported; however, its effect on myogenic activity of uterus and mechanism thereof is obscure. Present study was undertaken to unravel the mechanistic pathways of mercuric chloride (HgCl2)-induced myometrial contraction in rats. Isometric tension in myometrial strips of rats following in vitro exposure to HgCl2 was recorded using data acquisition system-based physiograph. HgCl2 produced concentration-dependent (10 nM–100 μM) uterotonic effect which was significantly (p < 0.05) reduced in Ca2+-free solution and inhibited in the presence of nifedipine (1 μM), a L-type Ca2+ channel blocker, thus suggesting the importance of extracellular Ca2+ and its entry through L-type calcium channels in HgCl2-induced myometrial contractions in rats. Cumulative concentration-response curve of HgCl2 was significantly (p < 0.05) shifted towards right in the presence of Y-27632 (10 μM), a Rho-kinase inhibitor, suggesting the involvement of Ca2+-sensitization pathway in mediating HgCl2-induced myometrial contraction. HgCl2-induced myometrial contraction was also significantly (p < 0.05) inhibited in the presence of methoctramine or para-fluoro-hexahydro-siladifenidol, a selective M2 and M3 receptor antagonists, respectively, which evidently suggest that mercury also interacts with M2 and M3 muscarinic receptors to produce myometrial contractions. U-73122 and GF-109203X, the respective inhibitors of PLC and PKC-dependent pathways, downstream to the receptor activation, also significantly (p < 0.05) attenuated the uterotonic effect of HgCl2 on rat uterus. Taken together, present study evidently reveals that HgCl2 interacts with muscarinic receptors and activates calcium signaling cascades involving calcium channels, Rho-kinase, protein kinase-C, and phospholipase-C pathways to exert uterotonic effect in rats.
KeywordsMercury Myometrium VDCC Calcium Muscarinic receptor PKC PLC Rho-kinase
Research work presented in this manuscript was undertaken in the research project funded by Indian Council of Agricultural Research, New Delhi, India, under Niche Area of Excellence Programme (Grant No. 10 (10)/2012-EPD dated 23rd march 2012) to Department of Veterinary Pharmacology and Toxicology, DUVASU, Mathura, India. Financial assistance from ICAR is thankfully acknowledged.
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Conflict of Interest
The authors declare that they have no conflict of interest.
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