Evidence for the involvement of histamine in the regulation of blood-brain barrier permeability.

Role of histaminergic mechanisms in the regulation of blood-brain barrier (BBB) was assessed in dog. Histamine increased the entry of sodium fluorescein from the blood to the cerebrospinal fluid (CSF) in a dose-dependent manner. Histamine receptor antagonists, mepyramine (H1) and metiamide (H2) per se did not affect the entry of dye in the CSF. Mepyramine failed to affect the change induced by histamine whereas metiamide completely blocked the histamine-induced entry of sodium fluorescein in CSF. 2-Methyl histamine, a specific H1-agonist, did not affect the barrier permeability. However, 4-methyl histamine, a specific H2 receptor agonist significantly increased the permeability of BBB. This increase was blocked by metiamide. Forskolin, a stimulant of adenylate cyclase, also increased the entry of dye in the CSF which could be significantly blocked by metiamide. It is concluded that histamine increases the permeability of BBB by affecting H2-receptors linked to adenylate cyclase.