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

1 Prostaglandins and the vasodilator neuropeptide, calcitonin-gene related peptide (CGRP), have both been implicated in the pathogenesis of migraine h eadache. 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 rece ptor agonist, carbaprostacyclin (cPGI(2)). These responses were extracellul ar calcium-dependent, and the PGE(2)-induced CGRP release was unaltered by inhibition of nitric oxide synthase (NOS), ATP receptor blockade, or the ad dition 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 increas es in CGRP release were observed in response to prostaglandin F-2x (PGF(2x) ) or the TP receptor selective agonist, U46619, or the EP3 receptor selecti ve agonist, GR63799X. 4 The selective DP receptor antagonist, BWA868C, antagonized the PGD(2)-, b ut not PGE(2)- or cPGI(2)-induced release. Furthermore, the EP1 selective a ntagonist, ZM325802, failed to antagonize the PGE(2)-induced CGRP release f rom these cells. 5 These data indicate that activation of DP, EP and IP receptors can each c ause CGRP release from trigeminal neurones, and suggest that the predominan t EP receptor subtype involved may be the EP2 receptor. Together with evide nce that the cyclo-oxygenase inhibitor, aspirin, particularly when administ ered intravenously is effective in treating acute migraine, these findings further suggest a role for prostaglandins in migraine pathophysiology.