Functional and molecular characterization of prostaglandin E 2 dilatory receptors in the rat craniovascular system in relevance to migraine

Introduction: Migraine pain is thought to involve an increase in trigeminal nerve terminal activity around large cerebral and meningeal arteries, leading to vasodilatation. Because prostaglandin E 2 (PGE 2 ) is elevated in cephalic venous blood during migraine attacks, and is also capable of inducing headache in healthy volunteers, we hypothesize that PGE 2 dilatory receptors, EP 2 and EP 4 , mediate the response. Materials and methods: By the use of specific agonists and antagonists, the dilatory effect of PGE 2 was characterized in rat cranial arteries by use of in vivo and in vitro methods. Furthermore, EP 2 and EP 4 quantitative messenger RNA (mRNA) receptor expression was studied in the rat craniovascular system. Results: Our results suggest that EP 4 , and to a lesser degree EP 2 , receptors mediate the dilatory effect of PGE 2 in the craniovascular system in rats. Thus, antagonism of these receptors might be of therapeutic relevance in migraine.