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

Apr 22, 2021Naunyn-Schmiedeberg's archives of pharmacology

Calcium signals control PGF2α-triggered uterine muscle contractions differently in water buffaloes

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Abstract

Myometrium of nonpregnant buffaloes is more sensitive to PGF-induced contractions than that of pregnant buffaloes.

Calcium signaling pathways play a differential role in PGF-induced contractions in myometrium of nonpregnant and pregnant buffaloes.
Nifedipine significantly reduces myometrial contraction to PGF in both nonpregnant and pregnant buffaloes.
Inhibitory effects of mibefradil and NNC 55-0396 on contractions are observed only in pregnant buffaloes.
Enhanced activation of TRPC3 channels and Rho-kinase pathways contributes to PGF-induced contractions in nonpregnant myometrium.
Pregnancy is associated with significant down-regulation of TRPC3 and Rho-A proteins, which may facilitate uterine relaxation.

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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 PGFas manifested by changes in mean integral tension (MIT) and tonicity. In the presence of nifedipine, myometrial contraction to PGFwas 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 Cainflux through nifedipine-sensitive L-type Ca-channels both in NP and pregnant, but T-type Cachannels seem to play a role only during pregnancy. Entry of extracellular Cais 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 PGFin 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 PGFwas observed in both NP and pregnant myometrium which suggests minor role of intracellular source of Cain mediating PGF-induced contractions in these tissues. 2α 2α 2α 2α 2α 2α 2+ 2+ 2+ 2+ 2+ 2+

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

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