Extra and intracellular calcium signaling pathway(s) differentially regulate histamine-induced myometrial contractions during early and mid-pregnancy stages in buffaloes (Bubalus bubalis)

- Early-pregnant buffaloes were more sensitive to uterotonic action of histamine.
- L- and T-type VDCC is the major gateway for extracellular Ca2+ entry.
- Histamine-induced contraction is dependent on both extracellular and intracellular Ca2+.
- Extracellular calcium plays major role in MP and intracellular calcium during EP.
- Role of PL-C more prominent in early pregnancy stage.

This study examines the differential role of calcium signaling pathway(s) in histamine-induced uterotonic action during early and mid-pregnancy stages in buffaloes. Compared to mid pregnancy, tonic contraction, amplitude and mean-integral tension were significantly increased by histamine to produce myometrial contraction during early pregnancy with small effects on phasic contraction and frequency. Although uterotonic action of histamine during both stages of pregnancy is sensitive to nifedipine (a L-type Ca2+ channels blocker) and NNC55-0396 (T-type Ca2+ channels blocker), the role of extracellular calcium seems to be more significant during mid-pregnancy as in this stage histamine produced only 9.38 ± 0.96% contraction in Ca2+ free-RLS compared to 21.60 ± 1.45% in uteri of early pregnancy stage. Intracellular calcium plays major role in histamine-induced myometrial contraction during early pregnancy as compared to mid pregnancy, as in the presence of cyclopiazonic acid (CPA) Ca2+-free RLS, histamine produced significantly higher contraction in myometrial strips of early-pregancy in comparison to mid-pregnancy (10.59 ± 1.58% and 3.13 ± 0.46%, respectively). In the presence of U-73122, the DRC of histamine was significantly shifted towards right with decrease in maximal effect (Emax) only in early pregnancy suggesting the predominant role of phospholipase-C (PL-C) in this stage of pregnancy.