Lowering extracellular pH evokes inositol polyphosphate formation and calcium mobilization.
Changing extracellular pH (pHo) from 7.4 to 6.1 increased [3H]inositol bis- and trisphosphates approximately 10- and 5-fold, respectively, in 15 s in human fibroblasts. [3H]Inositol phosphate increased less rapidly than the polyphosphates. Bradykinin similarly increased [3H]inositol phosphates. Shifting pHo from 7.4 to 6.0 evoked a large spike in cytosolic free Ca2+ [( Ca2+]i) which was primarily caused by the release of stored Ca2+. Changing pHo from 7.4 to 6.0 decreased cytoplasmic pH to approximately 7.0. Moderate decreases in intracellular pH had no effect on [Ca2+]i or 45Ca2+ efflux. Decreasing pHo strikingly increased 45Ca2+ efflux and decreased total cell Ca2+ similarly to bradykinin. Changing pHo from 7.4 to approximately 6.4 produced half-maximal effects on [Ca2+]i, 45Ca2+ efflux, and total Ca2+. Cycling pHo between 7.4 and 6.0 produced repetitive decreases and increases in total Ca2+. Bradykinin released the Ca2+ which was reaccumulated after an acid pulse indicating that Ca2+ had returned to the hormone-sensitive pool. Decreasing pHo also released stored Ca2+ from coronary endothelial, neuroblastoma, and umbilical artery muscle cells, but not from rat aortic smooth muscle or human epidermoid carcinoma (A431) cells. We suggest that lowering pHo stimulates a phosphoinositidase-coupled receptor by protonating a functional group with a pKa near 6.5.
Smith
J B
JB
Department of Pharmacology, School of Medicine, University of Alabama, Birmingham 35294.
Dwyer
S D
SD
Smith
L
L
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D012867:Skin / Q000378:metabolism; D013403:Sugar Phosphates / Q000096:biosynthesis*
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D002118:Calcium