Endothelial expression of the 5-hydroxytryptamine1B 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 ago, serotonin (5-hydroxytryptamine) acts as a neurotransmitter/modulator in the central nervous system and regulates local cerebral blood flow and vascular permeability through direct and indirect effects on intraparenchymal microvessels. Among the various 5-hydroxytryptamine receptors,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 microscopic 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 membrane-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 localization of the vascular 5-hydroxytryptamine,. receptor to periarteriolar myocytes,vas also confirmed, Such a dual localization in human brain microvessels suggests that the 5-hydroxytryptamine(1B) receptor might mediate opposite effects, vasodilatory and contractile, depending upon its activation by circulating or centrally released 5-hydroxytryptamine, It raises nem possibilities as regards 5-hydroxytryptamine effects on human brain microvessels in health and disease, and notably the triggering of migraine headache. (C) 1998 IBRO. Published by Elsevier Science Ltd.