Histamine receptors and neuropeptides in the cranial circulation

Sammanfattning: The sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) are present in human cerebral, meningeal and temporal arteries, as are peptides associated with the sympathetic (neuropeptide Y, NPY) and parasympathetic (vasoactive intestinal peptide, VIP) nervous system. NPY is a vasoconstrictor in cerebral and meningeal arteries and potentiates noradrenaline (NA) as a vasoconstrictor in temporal arteries. SP, CGRP and VIP act as potent vasodilators in all three craniovascular regions. The middle meningeal artery is more sensitive to SP compared to the cerebral and temporal arteries. For CGRP, the cerebral artery is the most sensitive and the meningeal artery shows the least potent response. In the rat, SP can release histamine from both dural and peritoneal mast cells. CGRP releases histamine from rat dural mast cells but not from peritoneal mast cells. The NK1-receptor antagonist FK888 blocks the SP-evoked histamine release and the CGRP-antagonist CGRP8-37 blocks the CGRP-evoked histamine release. NPY and VIP release only small amounts of histamine. The guinea-pig basilar artery is equipped with contractile H1-receptors and no dilatory histamine-receptors. The H1-receptor activation is coupled to dihydropyridine-sensitive Ca2+ channels. Histamine H1- and H2-receptors are present in human cerebral, meningeal and temporal arteries. The existence of H1- and H2-receptors in smooth muscle in these human vessels is confirmed by demonstrating the presence of mRNA encoding the two receptor proteins. The response of partially precontracted human cerebral, meningeal and temporal arteries to histamine in vitro is relaxation. This relaxation is partially mediated via an endothelial H1-receptor coupled to the production of NO, partially via a H2-receptor associated with the smooth muscle cells. In addition, there is evidence for a contractile H1-receptor at the smooth muscle cells. There are indications for the presence of H3-receptors in temporal arteries, but not in cerebral or meningeal arteries.