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


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.
Myren
Maja
M
Glostrup Hospital, University of Copenhagen, Denmark.
Baun
Michael
M
Ploug
Kenneth Beri
KB
Jansen-Olesen
Inger
I
Olesen
Jes
J
Gupta
Saurabh
S
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects / Q000503:physiopathology*; D015232:Dinoprostone / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000503:physiopathology*; D008881:Migraine Disorders / Q000503:physiopathology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics*; D014276:Trigeminal Nerve / Q000098:blood supply* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D044004:Xanthones / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011448:Prostaglandin Antagonists; D012333:RNA, Messenger; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D044004:Xanthones; C017759:9-(tetrahydro-2-furyl)-adenine; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D000527:Alprostadil; C048491:butaprost; D000225:Adenine; D015232:Dinoprostone