TY - JOUR
T1 - Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery
AU - Chan, Ka yi
AU - Baun, Michael
AU - de Vries, René
AU - Bogaerdt, Antoon
AU - Dirven, Clemens
AU - Danser, Jan
AU - Jansen-Olesen, Inger
AU - Olesen, Jes
AU - Villalon Herrera, Carlos M.
AU - Maassen van den Brink, Antoinette
AU - Gupta, Saurabh
PY - 2011
Y1 - 2011
N2 - Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC(1), VPAC(2) and PAC(1) 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 VPAC(1) receptor agonist ([Lys15, Arg16, Leu27]-VIP[1-7]-GRF[8-27]) were constructed in the absence or presence of the PAC(1) 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 E-max 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 VPAC(1), VPAC(2) and PAC(1) 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 VPAC(1) receptor agonist ([Lys15, Arg16, Leu27]-VIP[1-7]-GRF[8-27]) were constructed in the absence or presence of the PAC(1) 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 E-max 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 - Article
C2 - 20974589
SN - 0333-1024
VL - 31
SP - 181
EP - 189
JO - Cephalalgia
JF - Cephalalgia
IS - 2
ER -