EVIDENCE OF A DUAL ROLE OF ENDOGENOUS HISTAMINE IN ANGIOGENESIS

The specific activation of mast cells in situ causes vigorous local ma st-cell mediated angiogenesis (MCMA). The mast cell is a major source of histamine and, as recently reported, specific histamine H-1- and H- 2-membrane receptor antagonists are able individually to significantly suppress MCMA in rats, as assessed using the mesenteric window angiog enesis assay (MWAA). In addition to membrane receptors for histamine, a type of intracellular histamine receptors, designated H-ic, has been described. It is now demonstrated that the potent H-ic-receptor antag onist DPPE (N,N-diethyl-2-E4-(phenylmethyl)phenoxylethan HCl), adminis tered parenterally, stimulates MCMA significantly in rats, as quantifi ed by the MWAA. Although the target cell(s) are not known, there are s everal ways by which their H-ic receptors could be activated: uptake o f histamine released from mast cells, mobilization from preformed cyto plasmic and nuclear stores, and production of de novo histamine by his tidine decarboxylase activity. The fact that the occupancy by histamin e of H-1- and H-2-membrane receptors stimulates MCMA and the occupancy by histamine of H-ic inhibits MCMA suggests that endogenous histamine is capable of regulating angiogenesis by a dual mode of action. This is apparently the first report ascribing a dual role of this type in a ngiogenesis to a single molecule.