Characterization of the prostanoid receptor types involved in mediating calcitonin gene-related peptide release from cultured rat trigeminal neurones

被引:59
作者
Jenkins, DW [1 ]
Feniuk, W [1 ]
Humphrey, PPA [1 ]
机构
[1] Univ Cambridge, Dept Pharmacol, Glaxo Inst Appl Pharmacol, Cambridge CB2 1QJ, England
关键词
prostanoids; prostaglandin E-2; prostacyclin; migraine; calcitonin gene-related peptide; trigeminal ganglion; primary culture;
D O I
10.1038/sj.bjp.0704357
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine headache. We have used primary cultures of adult rat trigeminal neurones to examine the effects of prostanoids on CGRP release in vitro. 2 CGRP release was stimulated by prostaglandin E-2 (PGE(2)) and the IP receptor agonist, carbaprostacyclin (cPGI(2)). These responses were extracellular calcium-dependent, and the PGE(2)-induced CGRP release was unaltered by inhibition of nitric oxide synthase (NOS), ATP receptor blockade, or the addition of adenosine deaminase. 3 Increases in CGRP levels were also observed in response to prostaglandin D-2 (PGD(2)), and the EP2 receptor selective agonist, butaprost. No increases in CGRP release were observed in response to prostaglandin F-2x (PGF(2x)) or the TP receptor selective agonist, U46619, or the EP3 receptor selective agonist, GR63799X. 4 The selective DP receptor antagonist, BWA868C, antagonized the PGD(2)-, but not PGE(2)- or cPGI(2)-induced release. Furthermore, the EP1 selective antagonist, ZM325802, failed to antagonize the PGE(2)-induced CGRP release from these cells. 5 These data indicate that activation of DP, EP and IP receptors can each cause CGRP release from trigeminal neurones, and suggest that the predominant EP receptor subtype involved may be the EP2 receptor. Together with evidence that the cyclo-oxygenase inhibitor, aspirin, particularly when administered intravenously is effective in treating acute migraine, these findings further suggest a role for prostaglandins in migraine pathophysiology.
引用
收藏
页码:1296 / 1302
页数:7
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