ENDOTHELIAL EXPRESSION OF THE 5-HYDROXYTRYPTAMINE(1B) ANTIMIGRAINE DRUG RECEPTOR IN RAT AND HUMAN BRAIN MICROVESSELS

In addition to triggering vasoconstriction of peripheral blood vessels , which led to its discovery as a circulating neurohormone 50 years ag o, serotonin (5-hydroxytryptamine) acts as a neurotransmitter/modulato r in the central nervous system and regulates local cerebral blood flo w and vascular permeability through direct and indirect effects on int raparenchymal microvessels. Among the various 5-hydroxytryptamine rece ptors,which mediate these effects, particular attention has been paid to the 5-hydroxytryptamine(1B) and 5-hydroxytryptamine,, subtypes, as the preferred targets of modern antimigraine agents. Immunoelectron mi croscopic labeling of the 5-hydroxytryptamine,. receptor in rat brain parenchyma has revealed a distinct localization to the endothelium of microvessels, which mas predominantly cytoplasmic as opposed to membra ne-bound, contrary to that on preterminal unmyelinated axons [Riad et al. (1997) Soc. Neurosci. Abstr. 23, 1214], Similar observations have now been made in human cortical tissue, in which the expected localiza tion of the vascular 5-hydroxytryptamine,. receptor to periarteriolar myocytes,vas also confirmed, Such a dual localization in human brain m icrovessels suggests that the 5-hydroxytryptamine(1B) receptor might m ediate opposite effects, vasodilatory and contractile, depending upon its activation by circulating or centrally released 5-hydroxytryptamin e, It raises nem possibilities as regards 5-hydroxytryptamine effects on human brain microvessels in health and disease, and notably the tri ggering of migraine headache. (C) 1998 IBRO. Published by Elsevier Sci ence Ltd.