Actions of serum and plasma albumin on intracellular Ca2+ in human endothelial cells.
1. The effects of serum and plasma albumin on [Ca2+]i in human endothelial cells were examined using single-cell Ca2+ imaging. Two types of endothelial cell were used: human umbilical vein endothelial cells (HUVEC) in primary culture, and the endothelial-derived cell line ECV304. 2. Serum albumin caused a large and transient rise in [Ca2+]i, due to Ca2+ release from an IP3-sensitive internal store, followed by a maintained elevation in [Ca2+]i attributable to Ca2+ influx from the external medium. A half-maximal rise in [Ca2+]i was produced by a concentration of serum albumin of about 1 microgram ml-1. 3. The Ca(2+)-releasing action of serum albumin is abolished by methanol extraction and is therefore attributable to an attached polar lipid. A possible candidate is lysophosphatidic acid, known to be released from platelets during blood coagulation, which produced similar effects to those of serum albumin. 4. In HUVEC, plasma albumin caused a sustained decrease in [Ca2+]i from the mean resting level of 114 nM to 58 nM. No effect of plasma albumin was observed in ECV304 cells. 5. The decrease in [Ca2+]i caused by plasma albumin is due to an uptake into intracellular stores. The store loading substantially potentiates the action of Ca(2+)-releasing agonists such as histamine. 6. The results show that normal plasma albumin, which carries few lipids, lowers [Ca2+]i and potentiates the actions of Ca(2+)-releasing agonists by promoting Ca2+ uptake into intracellular stores. When converted to the serum form, by binding lysophosphatidic acid released during blood coagulation, albumin has a potent effect in elevating [Ca2+]i. Blood coagulation may therefore play a role in regulating vascular tone and capillary permeability.
Fuentes
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E
Department of Physiology, King's College London, Strand, UK.
Nadal
A
A
Jacob
R
R
McNaughton
P
P
D002118:Calcium / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism / Q000494:pharmacology; D008954:Models, Biological; D012709:Serum Albumin / Q000494:pharmacology*; D014471:Umbilical Veins
D008055:Lipids; D008246:Lysophospholipids; D012709:Serum Albumin; D006632:Histamine; D002118:Calcium