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 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 VPAC(1) 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.


CONCLUSIONS
The direct vasodilatory effect of VIP and PACAP might be less relevant than the central effect of this compound in migraine pathogenesis.
Erasmus Medical Center, The Netherlands.
Kayi Y
KY
Chan
Michael
M
Baun
René
R
de Vries
Antoon J
AJ
van den Bogaerdt
Clemens M F
CM
Dirven
Alexander H J
AH
Danser
Inger
I
Jansen-Olesen
Jes
J
Olesen
Carlos M
CM
Villalón
Antoinette
A
MaassenVanDenBrink
Saurabh
S
Gupta
D000328:Adult; D000368:Aged; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008576:Meningeal Arteries / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D018005:Receptors, Vasoactive Intestinal Peptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
C495401:ADCYAP1 protein, human; C110307:PG 97-269; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014665:Vasodilator Agents; C075647:pituitary adenylate-cyclase-activating-peptide (6-38); D014660:Vasoactive Intestinal Peptide