BQ-123, cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu), is a non-competitive antagonist of the actions of endothelin-1 in SK-N-MC human neuroblastoma cells.
SK-N-MC cells, derived from a human neuroblastoma, respond to endothelin (ET) peptides with an increase in the free intracellular calcium concentration. The response is biphasic, with the secondary plateau phase being abolished or reduced by removal of extracellular Ca2+ or by the presence of 100nM nitrendipine. Restoration of Ca2+ to the bathing solution in cells stimulated by ET-1 in the absence of Ca2+ caused the plateau to reappear. The order of potency of ET family peptides was ET-2 greater than or equal to sarafotoxin S6b greater than or equal to ET-1 much greater than ET-3, suggesting that ETA receptors mediate the response. Sarafotoxin S6c and the C-terminal hexapeptide endothelin (16-21) were inactive in these cells. [Ala1,3,11,15]ET-1, a linear analogue of ET-1 which has been suggested to be a selective ETB receptor agonist, was a weak competitive antagonist of the actions of ET-1 in these cells. However, BQ-123, recently introduced as a selective and competitive antagonist at ETA receptors, was a potent non-competitive antagonist of ET-1 giving a 50% reduction in the maximum response at 6nM.
Hiley
C R
CR
Marion Merrell Dow Research Institute, Strasbourg, France.
Cowley
D J
DJ
Pelton
J T
JT
Hargreaves
A C
AC
D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009447:Neuroblastoma; D009568:Nitrendipine / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D016232:Endothelins; D010456:Peptides, Cyclic; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; D009568:Nitrendipine; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D002118:Calcium