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We have reported that phospholipase C-\u03b31 (PLC\u03b31) plays a significant role in the hypoxia-induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in PASMCs and attendant HPV. In this study, we intended to determine molecular mechanisms for hypoxic Ca<jats:sup>2+<\/jats:sup>and contractile responses in PASMCs. Our data reveal that hypoxic vasoconstriction occurs in pulmonary arteries, but not in mesenteric arteries. Hypoxia caused a large increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in PASMCs, which is diminished by the PLC inhibitor U73122 and not by its inactive analog U73433 . Hypoxia augments PLC\u03b31-dependent inositol 1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>) generation. Exogenous ROS, hydrogen peroxide (H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>), increases PLC\u03b31 phosphorylation at tyrosine-783 and IP<jats:sub>3<\/jats:sub>production. IP<jats:sub>3<\/jats:sub>receptor-1 (IP<jats:sub>3<\/jats:sub>R1) knock-down remarkably diminishes hypoxia- or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>-induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Hypoxia or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>increases the activity of IP<jats:sub>3<\/jats:sub>Rs, which is significantly reduced in protein kinase C-\u03b5 (PKC\u03b5) knockout PASMCs. A higher PLC\u03b31 expression, activity, and basal [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>are found in PASMCs, but not in mesenteric artery smooth muscle cells from mice exposed to chronic hypoxia (CH) for 21 days. CH enhances H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>- and ATP-induced increase in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>in PASMCs and PLC-dependent, norepinephrine-evoked pulmonary vasoconstriction. In conclusion, acute hypoxia uniquely causes ROS-dependent PLC\u03b31 activation, IP<jats:sub>3<\/jats:sub>production, PKC\u03b5 activation, IP<jats:sub>3<\/jats:sub>R1 opening, Ca<jats:sup>2+<\/jats:sup>release, and contraction in mouse PASMCs; CH enhances PASM PLC\u03b31 expression, activity, and function, playing an essential role in pulmonary hypertension in mice.<\/jats:p>","DOI":"10.1152\/ajplung.00243.2017","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T12:38:45Z","timestamp":1517488725000},"page":"L724-L735","source":"Crossref","is-referenced-by-count":34,"title":["PLC\u03b31-PKC\u03b5-IP<sub>3<\/sub>R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells"],"prefix":"10.1152","volume":"314","author":[{"given":"Vishal R.","family":"Yadav","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, New 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