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-hydroxytryptamine1B and 5-hydroxytryptamine1D subtypes, as the preferred targets of modern antimigraine agents. Immunoelectron microscopic labeling of the 5-hydroxytryptamine1B receptor in rat brain parenchyma has revealed a distinct localization to the endothelium of microvessels, which was 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-hydroxytryptamine1B receptor to periarteriolar myocytes was also confirmed. Such a dual localization in human brain microvessels suggests that the 5-hydroxytryptamine1B receptor might mediate opposite effects, vasodilatory and contractile, depending upon its activation by circulating or centrally released 5-hydroxytryptamine. It raises new possibilities as regards 5-hydroxytryptamine effects on human brain microvessels in health and disease, and notably the triggering of migraine headache.
Riad
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M
Département de Pathologie et Biologie Cellulaire, Faculté de Médecine, Université de Montréal, Québec, Canada.
Tong
X K
XK
el Mestikawy
S
S
Hamon
M
M
Hamel
E
E
Descarries
L
L
D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008881:Migraine Disorders / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C470302:HTR1B protein, human; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin