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Calcium signaling cascades differentially regulate PGF2α-induced myometrial contractions in water buffaloes (Bubalus bubalis)

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Abstract

This study unravels the differential involvement of calcium signaling pathway(s) in PGF2α-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 PGF2α as manifested by changes in mean integral tension (MIT) and tonicity. In the presence of nifedipine, myometrial contraction to PGF2α 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 Ca2+ influx through nifedipine-sensitive L-type Ca2+-channels both in NP and pregnant, but T-type Ca2+ channels seem to play a role only during pregnancy. Entry of extracellular Ca2+ 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 PGF2α 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 Ca2+-free solution and cyclopiazonic acid (SERCA blocker), feeble contraction to PGF2α was observed in both NP and pregnant myometrium which suggests minor role of intracellular source of Ca2+ in mediating PGF2α-induced contractions in these tissues.

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Acknowledgements

Research work presented in this manuscript was supported by Indian Council of Agricultural Research (ICAR), New Delhi, India, under Niche Area of Excellence Programme (Grant No. 10 (10)/2012-EPD dated 23rd March 2012) to the Department of Veterinary Pharmacology and Toxicology, DUVASU, Mathura, India. Financial assistance by ICAR is thankfully acknowledged.

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Authors and Affiliations

  1. 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

    Abhishek Sharma, Udayraj P. Nakade, Raut Akash, Virendra Pratap Yadav, Soumen Choudhury, Pooja Jaitley, Vipin Sharma & Satish Kumar Garg

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  1. Abhishek Sharma
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  2. Udayraj P. Nakade
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Contributions

AS, UPN, and VS conducted the functional experiments; PJ, RA, VPY, and SC performed Western blot and IHC; SC and AS analyzed the data; and SC and SKG conceptualized the experiments and wrote the MS. All the authors have read and approved the manuscript. All data were generated in-house and that no paper mill was used.

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Correspondence to Satish Kumar Garg.

Ethics declarations

Uterus of animals is a nonedible part and is thrown away by the slaughterers/butchers as bio-waste. Therefore, uteri of buffaloes were collected from the slaughter house or butcher’s shops. Any biological experimental material collected from butcher’s shop or slaughter house is not covered under the “Guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals” of Govt. of India (as resolved by Institutional Animal Ethics Committee in its meeting held on 16.09.2016 vide circulation No. 110/IAEC/16/40/2).

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Sharma, A., Nakade, U.P., Akash, R. et al. Calcium signaling cascades differentially regulate PGF2α-induced myometrial contractions in water buffaloes (Bubalus bubalis). Naunyn-Schmiedeberg's Arch Pharmacol 394, 1651–1664 (2021). https://doi.org/10.1007/s00210-021-02084-4

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