Mechanism of mastoparan-induced EDRF release from pulmonary artery endothelial cells.
Mastoparan is a wasp venom peptide that activates G-proteins, certain classes of which are involved in the release of endothelium-derived relaxing factor (EDRF). In the present study, we investigated whether this peptide might be a useful tool with which to elucidate the signal transduction pathways responsible for EDRF release from pulmonary artery endothelium. Mastoparan (10-50 micrograms/ml) elicited an increase in endothelial cell cytosolic free calcium concentration ([Ca2+]i) and EDRF release in a concentration-dependent manner. Both effects were dependent on Ca2+ influx, as they were inhibited by removal of extracellular Ca2+. In addition, when endothelial cells were suspended in Ca(2+)-free buffer, mastoparan inhibited ATP-induced increases in [Ca2+]i, presumably by depleting intracellular Ca2+ stores. More importantly, mastoparan also caused the release of fura-2 from dye-loaded endothelial cells, unlike ATP, which did not affect fura-2 loss. These data indicate that although mastoparan may act on G-proteins to elicit release of Ca2+ from intracellular stores, the primary mechanism of action responsible for mastoparan's ability to elicit EDRF release is an increase in cell membrane permeability followed by an influx of extracellular Ca2+.
Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville.
W R
WR
Tracey
M J
MJ
Peach
D000818:Animals; D002021:Buffers; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016257:Fura-2; D036341:Intercellular Signaling Peptides and Proteins; D009569:Nitric Oxide / Q000378:metabolism*; D009994:Osmolar Concentration; D010455:Peptides; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D014862:Wasp Venoms / Q000494:pharmacology*
D002021:Buffers; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D009569:Nitric Oxide; C037500:mastoparan; D002118:Calcium; D016257:Fura-2