The in vivo effect of VIP, PACAP-38 and PACAP-27 and mRNA expression of their receptors in rat middle meningeal artery.
The parasympathetic nervous system is probably involved in migraine pathogenesis. Its activation releases a mixture of signalling molecules including vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP), which subsequently stimulate VPAC(1), VPAC(2) and PAC(1) receptors. The objective of the present study was to investigate the in vivo effect of VIP, PACAP-27, PACAP-38, the selective VPAC(1) agonist ([Lys15, Arg16, Leu27]-VIP(1-7)-GRF(8-27)) and a PAC(1) agonist, maxadilan on rat middle meningeal artery (MMA) diameter using the closed cranial window model. Selective antagonists were used for further characterization of the responses. Reverse transcriptase-polymerase chain reaction experiments were also conducted to determine expression of mRNA of PACAP receptors in the MMA. The results showed that VIP, PACAP-38, PACAP-27 and the VPAC(1) specific agonist evoked significant dilations with the rank order of potency; VIP = PACAP-38 > PACAP-27 = [Lys15, Arg16, Leu27]-VIP(1-7)-GRF(8-27). Significant inhibition of dilation was only observed for the VPAC(1) antagonist PG97-269 on PACAP-38-induced dilation of MMA. The VPAC(2) antagonist PG99-465 and PAC(1) antagonist PACAP(6-38) did not significantly block VIP- or PACAP-induced dilation. Expression of mRNA of all three receptors was detected in the MMA. In conclusion, the VPAC(1) receptor seems to be predominant in mediating MMA dilation. A selective VPAC(1) antagonist may be a candidate molecule in the treatment of migraine headache.
Boni
L J
LJ
Department of Neurology, Glostrup Research Institute, Glostrup Hospital, Glostrup, Denmark. louisejuhl@gmail.com
Ploug
K B
KB
Olesen
J
J
Jansen-Olesen
I
I
Gupta
S
S
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D008576:Meningeal Arteries / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide