Serotonin, norepinephrine, and histamine mediation of endothelial cell barrier function in vitro.
The effects of serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE), and histamine on endothelial cell barrier function were examined in vitro. Bovine aortic endothelial (BAE) cells grown to confluence on microcarriers formed a measurable barrier to the passage of a trypan blue dye-bovine serum albumin conjugate (TB-BSA) from the culture medium into the microcarrier matrix. Vascular smooth muscle (VSM) cells or Swiss 3T3 fibroblasts impeded TB-BSA diffusion only 42% and 56%, respectively, relative to BAE cells. These results suggest that barrier formation may be an endothelial cell-specific phenomenon. Treatment of BAE cells with histamine was associated with 2- to 3-fold increases in the rate of TB-BSA diffusion. In contrast, treatment with 5-HT or NE at concentrations ranging from normal to pathophysiological circulating plasma levels significantly impeded TB-BSA diffusion by up to 43% and 33%, respectively, relative to untreated controls. The barrier-modulating effects of the vasoactive amines were dose-dependent, cell-specific, and in some cases appear to be receptor-mediated. These results are consistent with previous reports that histamine increases vascular permeability in part by affecting diffusion between endothelial cells; they support the hypothesis that 5-HT and NE contribute to the maintenance of the endothelial barrier in vivo.
D000818:Animals; D001011:Aorta; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D004058:Diffusion; D004155:Diphenhydramine / Q000494:pharmacology; D004727:Endothelium / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D007650:Ketanserin; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014343:Trypan Blue / Q000378:metabolism
D010880:Piperidines; D010643:Phenoxybenzamine; D012710:Serum Albumin, Bovine; D012701:Serotonin; D006632:Histamine; D004155:Diphenhydramine; D007650:Ketanserin; D011433:Propranolol; D014343:Trypan Blue; D009638:Norepinephrine