Histamine receptors of the microvascular endothelium revealed in situ with a histamine-ferritin conjugate: characteristic high-affinity binding sites in venules.

Abstract

Histamine covalently bound to glutaraldehyde-activated ferritin was prepared as either monomers or as small aggregates of -0 .05 to 0.15 p,m Diam, suitable for electron microscopic detection of histamine cellular binding sites. The histamine-ferritin conjugates (MF) maintain the histamine capability to induce the opening of endothelial junctions in venules. To investigate the distribution of histamine receptors in the vascular endothelium, monomers or aggregates of MF were perfused in situ (mice), and various vascular beds, particularly that of the diaphragm, were fixed and processed for electron microscopy . The conjugate was preferentially bound on restricted areas of luminal endothelial cell plasmalemma especially in regions rich in filaments, and near the junctions between endothelial cells. The density of histamine binding sites was characteristically high in venules; it occurred to a much lesser extent in arterioles, veins, and muscular arteries whereas capillaries and aorta showed the lowest values . A similar distribution was obtained after perfusion of H, or H 2 receptor agonists coupled to ferritin (2-pyridylethylamine-ferritin [PF], or 4-methylhistamine-ferritin [MF], respectively) . The binding specificity was assessed through control experiments with either native or activated ferritin or by competition with histamine. The findings suggest that histamine receptors are largely represented in the cell membrane of the vascular endothelium, particularly in venules. Experiments using specific H, and H2 receptor agonists (PF and MF) and antagonists (mepyramine and cimetidine) indicate that the venular endothelium contains mainly H 2 receptors.

Induction, differentiation, and remodeling of blood vessels after transplantation of Bcl-2-transduced endothelial cells

“…Whereas normal, unstimulated vascular ECs retain large macromolecules under resting conditions, leakage of macromolecules may be triggered by stimuli such as histamine, VEGF, or TNF. Histamine rapidly induces a leak in the venular endothelium (20), which expresses higher levels of the H1 receptor (21). To test whether the Bcl-2-HUVECs were responsive to histamine, we administered 70-kDa FITC-dextran i.v., followed by histamine or saline, injected locally to the site of the implant 10 min before harvest.…”

Angiopoietin 1 causes vessel enlargement, without angiogenic sprouting,during a critical developmental period

“…Functionally, venules are most leaky to plasma proteins under baseline conditions and are the site of inflammation-induced plasma leak (Majno et al, 1969). Venular endothelial cells have a distinct molecular profile, including increased expression of P-selectin, von Willebrand factor (Thurston et al, 2000a), and receptors for inflammatory mediators (Bowden et al, 1994;Heltianu et al, 1982). In addition, venules are the segment most likely to sprout during angiogenesis (Folkman, 1982;Phillips et al, 1991).…”

Role of veins and cerebral venous pressure in disruption of the blood-brain barrier.

“…1415 This finding may be related to a greater density of receptor sites in venules for mediators of inflammation. 16 Also, oxygen radicals may play a role in disruption of the BBB in venules during acute hypertension. Previous studies" have not examined effects of acute hypertension on cerebral venules, but findings in other tissues 17 indicate that oxygen radicals increase microvascular permeability exclusively around post-capillary venules.…”