Role of Ca2+ and Mg2+ for endothelial permeability of water and albumin in vitro.
The permeability of endothelial monolayers grown on a polycarbonate filter membrane and continuously exposed to a hydrostatic pressure of 10 cm H2O was studied. The ionophores A23187 and ionomycin dose dependently (0.1-10 microM) enhanced the hydraulic conductivity of sealed endothelial cell monolayers 10 to 15-fold, at the same time the reflection coefficient of albumin dropped from 0.75 to 0.2. The effects of A23187 were dependent on extracellular Ca2+. In the absence of Ca2+, however, Mg2+ could substitute for Ca2+. Phase contrast- and scanning electron-microscopy showed that the A23187-induced effects were accompanied by gap-formation in the intercellular clefts. These gaps probably are the sites which allowed enhanced fluid exchange. Ionophore-induced effects on permeability could be modified by antagonists of calmodulin function and of arachidonate liberation and metabolism. The data suggest that alterations of endothelial Ca2+-homeostasis induce metabolic events which result in an increased permeability of an endothelial monolayer.
Suttorp
N
N
Division of Clinical Pathophysiology and Experimental Medicine/Department of Internal Medicine, Justus Liebig University, Giessen, Federal Republic of Germany.
Fuchs
T
T
Seeger
W
W
Wilke
A
A
Drenckhahn
D
D
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001834:Body Water / Q000378:metabolism*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004987:Ethers / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006874:Hydrostatic Pressure; D015759:Ionomycin; D007476:Ionophores / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism / Q000502:physiology*; D008567:Membranes, Artificial; D010539:Permeability; D013552:Swine
D000418:Albumins; D001095:Arachidonic Acids; D002147:Calmodulin; D004987:Ethers; D007476:Ionophores; D008567:Membranes, Artificial; D000001:Calcimycin; D015759:Ionomycin; D008274:Magnesium; D002118:Calcium