Modulation of arachidonic acid release and membrane fluidity by albumin in vascular smooth muscle and endothelial cells.
Albumin is the major plasma protein circulating in blood. Albumin potently decreases capillary permeability, although the mechanisms are not understood completely. Albumin also effectively binds arachidonic acid (AA), which increases capillary permeability. To investigate the interactions of BSA and AA with the cell membrane, the effect of these substances on [3H]AA release and membrane fluidity was studied in vascular myocytes and endothelial cells. BSA (0.2 and 1 mg . mL-1) stimulated a significant release of [3H]AA from both intact rat aorta and cultured smooth muscle cells. This effect was not mimicked by gamma-globulin or myoglobin (both 1 mg . mL-1) in intact tissue. BSA, but not gamma-globulin and myoglobin, decreased the membrane fluidity (assessed as changes in the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3, 5-hexatriene) in a concentration-dependent manner with a half-maximum concentration between 0.007 and 0.4 mg . mL-1 in both freshly isolated and cultured rat aortic myocytes and human umbilical vein endothelial cells. AA (1 to 200 micromol/L) caused the opposite effect, increasing membrane fluidity and antagonizing the effect of BSA. BSA modified at its arginine residues, which are thought to be important in AA binding, did not stimulate [3H]AA release and was significantly less potent than native BSA in altering the membrane fluidity. The effect of BSA can be explained by a high-affinity binding of AA to the protein and extraction of AA from the cell membrane. The interaction between BSA and AA could play a role in the regulation of vascular permeability.
Beck
R
R
Department of Pharmacology, UMDS of Guy's and St Thomas's Hospitals, St Thomas's Campus, London, UK.
Bertolino
S
S
Abbot
S E
SE
Aaronson
P I
PI
Smirnov
S V
SV
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000494:pharmacology*
D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D002118:Calcium