Glucocorticoid-mediated alterations in fluidity of rabbit cardiac muscle microvessel endothelial cell membranes: influences on eicosanoid release.
Experiments were conducted to determine effects of the synthetic glucocorticoid, dexamethasone, on the lipid fluidity of cultured rabbit cardiac muscle microvessel endothelial cells and the possible role(s) for altered fluidity in the steroid inhibition of cellular eicosanoid production. Following a sixteen hour exposure to 10(-7) M dexamethasone, membranes prepared from treated cells exhibited a decreased fluidity compared to their control counterparts, as assessed by steady-state fluorescence polarization techniques using 1,6-diphenyl-1,3,5-hexatriene (DPH). Examination of the effects of temperature on the anisotropy values of DPH using Arrhenius plots revealed consistent differences in the steroid treated cells over the entire temperature range (40-5 degrees C). These dexamethasone-dependent fluidity changes were associated with increases in the cholesterol/phospholipid ratio of membrane lipids. Restoration of membrane fluidity to control values with the fluidizing agent, 2-(2-methoxyethoxy)ethyl-8-(cis- 2-n-octylcyclopropyl)octanoate (A2C), partially reversed dexamethasone induced inhibition of A23187-stimulated eicosanoid release. These observations suggest that at least part of dexamethasone's inhibitory actions on eicosanoid generation in microvessel endothelial cells are mediated by alterations in membrane composition and fluidity.
Gerritsen
M E
ME
Department of Physiology, New York Medical College, Valhalla.
Schwarz
S M
SM
Medow
M S
MS
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D007700:Kinetics; D008833:Microcirculation; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D013816:Thermodynamics
D011453:Prostaglandins; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D011464:Epoprostenol; D015232:Dinoprostone