Mechanism of phospholipase C-induced release of EDRF from pulmonary artery endothelium
| Autor: | W. R. Tracey, Roger A. Johns, Michael J. Peach, G. Romero |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_specialty
Membrane permeability Fura-2 Glycosylphosphatidylinositols Physiology Pulmonary Artery Phospholipase Nitric Oxide Phosphatidylinositols Muscle Smooth Vascular chemistry.chemical_compound Internal medicine medicine Extracellular Animals Phosphatidylinositol Cyclic GMP Manganese Phospholipase C Hydrolysis Osmolar Concentration Endothelium-derived relaxing factor Cell Biology Endocrinology chemistry Type C Phospholipases Biophysics Calcium Endothelium Vascular Glycolipids Intracellular |
| Zdroj: | American Journal of Physiology-Cell Physiology. 261:C927-C935 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.1991.261.5.c927 |
| Popis: | The mechanism of phospholipase (PL) C-induced release of endothelium-derived relaxing factor (EDRF) was investigated. Bovine pulmonary artery endothelial cells (BPAEC) were treated with phosphatidylinositol (PI)-selective PLCs, nonselective PLCs, or a nonselective PLD. PI-PLCs elicited PI-glycan anchor hydrolysis but did not alter either intracellular Ca2+ ([Ca2+]i) in fura-2-loaded BPAEC or EDRF production in BPAEC-vascular smooth muscle cocultures. In contrast, non-selective PLCs increased [Ca2+]i, an effect prevented by prior exposure to the PLCs, and EDRF production in a time- and concentration-dependent manner. Antibodies raised against PI-glycan anchors did not alter, while heat denaturation abolished, the PLC-dependent effects. Removal of extracellular Ca2+ with [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid both prevented and reversed PLC-stimulated increases in [Ca2+]i and inhibited EDRF production. Although Mn2+ quenched PLC-induced increases in fura-2 fluorescence, high PLC concentrations elicited significant dye loss from fura-2-loaded BPAEC. We conclude that the effects of exogenous PLC on EDRF production are not dependent on release of a membrane PI-glycan-linked moiety. Rather, the PLC actions are mediated by a graded increase in cell membrane permeability, probably related to pore formation by the hemolytic activity of the enzyme, followed by an influx of extracellular Ca2+. |
| Databáze: | OpenAIRE |
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