Endothelin mobilizes Ca2+ from a caffeine- and ryanodine-insensitive intracellular pool in rat atrial cells.
Endothelin-1 is a powerful inotropic peptide for the rat atrium. Its action can develop in the absence of L-type Ca2+ channel activity provided that the external Ca2(+)-concentration has been raised to supraphysiological concentrations. Endothelin stimulates phosphatidylinositol hydrolysis in new born rat atrial cells via a mechanism that is insensitive to pertussis toxin. The diacylglycerol/protein kinase C signaling pathway cannot account for the contractile action of endothelin but its activation by phorbol esters induces a partial desensitization of phospholipase C activity. Endothelin-1 and the related peptides, endothelin-2, endothelin-3, and sarafotoxin S6b, raise intracellular Ca2+ levels in rat atrial cells. The actions of endothelin-1, endothelin-2, and sarafotoxin on [Ca2+]i are mutually exclusive, suggesting that they act at the same receptor site. The rise in [Ca2+]i induced by endothelins results both from the mobilization of intracellular stores and from Ca2+ entry through the sarcolemma via a pathway that is not voltage-dependent L-type Ca2+ channels. The Ca2+ store that is mobilized in response to endothelin retains its Ca2+ content when cells were incubated for long periods of time in a 50 nM Ca2+ solution. It is insensitive to caffeine and ryanodine. These two properties distinguish it from the sarcoplasmic reticulum. Contraction experiments in which the pacing rate has been altered to favor Ca2+ accumulation into terminal cisternae of the sarcoplasmic reticulum also suggest that the Ca2+ load of the sarcoplasmic reticulum is increased in endothelin treated rat atria.
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Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 Centre National de la Recherche Scientifique, Valbonne, France.
Breittmayer
J P
JP
Marsault
R
R
Frelin
C
C
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D002110:Caffeine / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D004789:Enzyme Activation; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D012433:Ryanodine / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D010738:Type C Phospholipases / Q000378:metabolism
D000470:Alkaloids; D015220:Calcium Channels; D016232:Endothelins; D010455:Peptides; D012433:Ryanodine; D002110:Caffeine; D007294:Inositol; D010738:Type C Phospholipases