Lowering Extracellular pH Evokes Inositol Polyphosphate Formation and Calcium Mobilization

• Published in: The Journal of biological chemistry Vol. 264; no. 15; pp. 8723 - 8728
• Main Authors: Smith, J B, Dwyer, S D, Smith, L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 25.05.1989; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Biological and medical sciences; calcium; Calcium - metabolism; Cell physiology; Cells, Cultured; Cytosol - metabolism; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Hydrogen-Ion Concentration; Inositol Phosphates - biosynthesis; inositol polyphosphates; Kinetics; Membrane and intracellular transports; Molecular and cellular biology; Skin - metabolism; Sugar Phosphates - biosynthesis; Human; Cell culture; Calcium; Radiolabelling; PH; Ion transport; Fibroblast; Cell surface
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)81853-1

Changing extracellular pH (pHo) from 7.4 to 6.1 increased [3H]inositol bis- and trisphosphates ∼ 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 ∼ 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 ∼ 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.