Endothelin-3 reduces Ca(2+)-uptake and Ca2+ content of platelet internal stores.
In stimulated platelets, endothelin-3 (ET-3) has been previously shown to attenuate Ca2+ mobilization. Using the calcium indicator chlortetracycline, the present study demonstrates that 0.5 microM ET-3 produced a 24% reduction in the Ca2+ pool mobilized by A23187. ET-3 up to 1 microM dose-dependently decreased the initial velocity and steady state value of 45Ca(2+)-uptake into platelet membrane vesicules (p < 0.001). In addition, ET-3 partially reversed the inhibitory effects of half maximally effective concentrations of thapsigargin and 2,5-di-(t-butyl)-1,4-benzohydroquinone, two specific inhibitors of the sarco/endoplasmic reticulum Ca(2+)-ATPases. These results suggest that ET-3 is functionally coupled to Ca(2+)-pumps of the dense tubular system. Based on these findings, we propose that ET-3 decreases the activity of Ca(2+)-pumps in the dense tubular system which accumulates less Ca2+, leading to lowered Ca2+ release in response to agonists.
Astarie-Dequeker
C
C
Department of Pharmacology, CNRS URA 1482, Descartes University, Necker Medical School, Paris, France.
Pernollet
M G
MG
Le Breton
G
G
Devynck
M A
MA
D000704:Analysis of Variance; D001693:Biological Transport, Active / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D002751:Chlortetracycline; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D010545:Peroxides / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D016232:Endothelins; D010545:Peroxides; D017382:Reactive Oxygen Species; D000001:Calcimycin; D020122:tert-Butylhydroperoxide; D013917:Thrombin; D002118:Calcium; D002751:Chlortetracycline