Stimulation of phospholipase C in cultured microvascular endothelial cells from human frontal lobe by histamine, endothelin and purinoceptor agonists

Endothelin

“…The latter are particularly sensitive to ET-1 and provide the therapeutic rationale for blocking the actions of the peptide, which is thought to be a mediator of cerebrovascular disorders including delayed vasospasm associated with subarachnoid hemorrhage and stroke. In contrast to the periphery, both ligand binding ( Yamaga et al, 1995 ) and functional studies suggest that human brain endothelial cells isolated from capillaries (diameter <10 µ m) that form the blood-brain barrier and from larger microvessels express ET A receptors linked to phospholipase C and IP 3 accumulation ( Stanimirovic et al, 1994 ; Spatz et al, 1997 ) possibly functioning to increase capillary permeability, leading to edema ( Purkiss et al, 1994 ). These studies used a comprehensive range of agonists and antagonists to show ET A -mediated responses, but this intriguing finding has not been explored further.…”

Evidence of promiscuous endothelial binding by P lasmodium falciparum ‐infected erythrocytes

“…The tetraspanins CD9 and CD151, multidrug-resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), the histamine H1 receptor (HRH1), oxidized low-density lipoprotein receptor 1 (LOX1) and vascular adhesion protein 1 (VAP-1) as well as truncated forms of tumour necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) and the erythropoietin receptor (EPOR) were expressed in glycosaminoglycan-deficient Chinese hamster ovary (CHO-745) cells. All have been shown to be expressed on human brain endothelial cells (Cordon-Cardo et al, 1989;Rossler et al, 1992;Salmi et al, 1993;Purkiss et al, 1994;Sawamura et al, 1997;Sincock et al, 1997;Dombrowski et al, 2001;Kadhim et al, 2006;Wosik et al, 2007;Medana et al, 2009). Tagged with green fluorescent protein (GFP) at their intracellular domains, the proteins were localized to the cell membrane by microscopy, and extracellular exposure was confirmed using non-permeabilized cells probed with specific antibodies; exceptions were LOX1, which was not GFP labelled but shown to be surface expressed by antibody staining, and MRP2, for which no antibodies or antisera are available directed to extracellular domains but which showed a characteristic GFP fluorescence at the outer cell membrane (Fig.…”

The Cerebral Microcirculation

“…As is the cased with bradykinin, 5HT operates through elevation of intracellular free calcium in endothelial cells. Elevations in intracellular calcium are also responsible for increased BBB permeability following exposure to adenosine nucleotides via activation of P2Y 2 purinoceptors [124,[129][130][131] . Histamine, released from histaminegic neurons, along with other sources, can increase BBB permeability [127] .…”