Endothelin-B receptor-mediated Ca2+ signaling in human melanocytes.
The mechanism of an endothelin-1- (ET-1-) induced intracellular Ca2+ ([Ca2+]i) increase and the receptor subtype(s) responsible for this effect in single human melanocytes were studied using fura-2/AM. ET-1 induced a transient increase in [Ca2+]i in a concentration-dependent manner. The transient [Ca2+]i increase was followed by a sustained plateau level of [Ca2+]i which was higher than the initial [Ca2+]i level. IRL-1620, a specific ET-B receptor agonist, increased [Ca2+]i in a dose-dependent manner. BQ-788, a specific ET-B receptor antagonist, abolished the ET-1-induced [Ca2+]i increase, but BQ-123, a specific ET-A receptor antagonist, failed to prevent it. U73122, an inhibitor of phospholipase C (PLC), inhibited the ET-1-induced [Ca2+]i rise in a dose-dependent manner. Prior depletion of intracellular Ca2+ stores with thapsigargin, an inhibitor of Ca2+-ATPase of the endoplasmic reticulum, abolished the ET-1-induced Ca2+ transient, whereas removal of extracellular Ca2+ with EGTA eliminated the sustained rise. These results suggest that in cultured human melanocytes the binding of ET-1 to ET-B receptors and the subsequent activation of PLC mediate ET-1-induced [Ca2+]i increase. The transient [Ca2+]i increase is attributed to mobilization of Ca2+ from inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores, and the sustained [Ca2+]i level may be related to the influx of extracellular Ca2+.
Kang
H Y
HY
Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea, 442-749.
Kang
W H
WH
Lee
C
C
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D008544:Melanocytes / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000502:physiology*; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D004963:Estrenes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011760:Pyrrolidinones; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C074308:sovateltide; D004533:Egtazic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium