Functional and molecular characterization of prostaglandin E2 dilatory receptors in the rat craniovascular system in relevance to migraine

• Published in: Cephalalgia 2010-09, Vol.30 (9), p.1110-1122
• Main Authors: Myren, Maja, Baun, Michael, Ploug, Kenneth Beri, Jansen-Olesen, Inger, Olesen, Jes, Gupta, Saurabh
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Alprostadil - analogs & derivatives; Alprostadil - pharmacology; Animals; Cerebral Arteries - drug effects; Cerebral Arteries - physiopathology; Dinoprostone - pharmacology; Enzyme Inhibitors - pharmacology; Male; Meningeal Arteries - drug effects; Meningeal Arteries - physiopathology; Migraine Disorders - physiopathology; Prostaglandin Antagonists - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Prostaglandin E, EP2 Subtype - agonists; Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors; Receptors, Prostaglandin E, EP2 Subtype - genetics; Receptors, Prostaglandin E, EP4 Subtype - agonists; Receptors, Prostaglandin E, EP4 Subtype - antagonists & inhibitors; Receptors, Prostaglandin E, EP4 Subtype - genetics; RNA, Messenger - metabolism; Trigeminal Nerve - blood supply; Trigeminal Nerve - physiopathology; Vasodilation - drug effects; Vasodilation - physiology; Xanthones - pharmacology
• ISSN: 0333-1024; 1468-2982
• DOI: 10.1177/0333102409357957

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 E2 (PGE2) is elevated in cephalic venous blood during migraine attacks, and is also capable of inducing headache in healthy volunteers, we hypothesize that PGE2 dilatory receptors, EP2 and EP4, mediate the response. Materials and methods: By the use of specific agonists and antagonists, the dilatory effect of PGE2 was characterized in rat cranial arteries by use of in vivo and in vitro methods. Furthermore, EP2 and EP4 quantitative messenger RNA (mRNA) receptor expression was studied in the rat craniovascular system. Results: Our results suggest that EP4, and to a lesser degree EP2, receptors mediate the dilatory effect of PGE2 in the craniovascular system in rats. Thus, antagonism of these receptors might be of therapeutic relevance in migraine.