TY - JOUR
T1 - Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery
AU - Chan, Kayi Y
AU - Baun, Michael
AU - de Vries, René
AU - van den Bogaerdt, Antoon J
AU - Dirven, Clemens M F
AU - Danser, Alexander H J
AU - Jansen-Olesen, Inger
AU - Olesen, Jes
AU - Villalón, Carlos M
AU - MaassenVanDenBrink, Antoinette
AU - Gupta, Saurabh
PY - 2011/2
Y1 - 2011/2
N2 - Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC1, VPAC2 and PAC1 receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries. Methods: Concentration response curves to PACAP38, PACAP27, VIP and the VPAC1 receptor agonist ([Lys15,Arg16,Leu27]-VIP[1-7]- GRF[8-27]) were constructed in the absence or presence of the PAC1 receptor antagonist PACAP6-38 or the VPAC1 receptor antagonist, PG97269. mRNA expression was measured using qPCR. Results: PACAP38 was less potent than VIP in both arteries. Both peptides had lower potency and efficacy in meningeal than in coronary arteries, while mRNA expression of VPAC 1 receptor was more pronounced in meningeal arteries. PACAP6-38 reduced the Emax of PACAP27, while PG97269 right-shifted the VIP-induced relaxation curve only in the coronary arteries. Conclusion: The direct vasodilatory effect of VIP and PACAP might be less relevant than the central effect of this compound in migraine pathogenesis.
AB - Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC1, VPAC2 and PAC1 receptors in human meningeal (for their role in migraine) and coronary (for potential side effects) arteries. Methods: Concentration response curves to PACAP38, PACAP27, VIP and the VPAC1 receptor agonist ([Lys15,Arg16,Leu27]-VIP[1-7]- GRF[8-27]) were constructed in the absence or presence of the PAC1 receptor antagonist PACAP6-38 or the VPAC1 receptor antagonist, PG97269. mRNA expression was measured using qPCR. Results: PACAP38 was less potent than VIP in both arteries. Both peptides had lower potency and efficacy in meningeal than in coronary arteries, while mRNA expression of VPAC 1 receptor was more pronounced in meningeal arteries. PACAP6-38 reduced the Emax of PACAP27, while PG97269 right-shifted the VIP-induced relaxation curve only in the coronary arteries. Conclusion: The direct vasodilatory effect of VIP and PACAP might be less relevant than the central effect of this compound in migraine pathogenesis.
U2 - 10.1177/0333102410375624
DO - 10.1177/0333102410375624
M3 - Journal article
SN - 0333-1024
VL - 31
SP - 181
EP - 189
JO - Cephalalgia
JF - Cephalalgia
IS - 2
ER -