Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery
Objective: We pharmacologically characterized pituitary adenylate cyclase-activating polypeptides (PACAPs), vasoactive intestinal peptide (VIP) and the VPAC1, VPAC2and PAC1receptors 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 VPAC1receptor agonist ([Lys15,Arg16,Leu27]-VIP[1-7]- GRF[8-27]) were constructed in the absence or presence of the PAC1receptor antagonist PACAP6-38 or the VPAC1receptor 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 VPAC1receptor was more pronounced in meningeal arteries. PACAP6-38 reduced the Emaxof 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.
|Keywords||PAC1, PACAP38, VIP, VPAC1, VPAC2|
|Persistent URL||dx.doi.org/10.1177/0333102410375624, hdl.handle.net/1765/31542|
Chan, K.Y, Baun, M, de Vries, R, van den Bogaerdt, A, Dirven, C.M.F, Danser, A.H.J, … Gupta, S. (2011). Pharmacological characterization of VIP and PACAP receptors in the human meningeal and coronary artery. Cephalalgia: an international journal of headache, 31(2), 181–189. doi:10.1177/0333102410375624