VIP and PACAP receptor pharmacology: a comparison of intracellular signaling pathways.
VIP/PACAP receptor activation stimulates the production of [cAMP]i and [Ca2+]i by coupling to independent G-protein subunits, although agonist potencies for the different transduction pathways appear to differ. Using CHO-K1 cells stably expressing the human VIP/PACAP receptors (hVPAC1R, hVPAC2R, and hPAC1R), functional assays ([cAMP]i and [Ca2+]i) were established and the receptor pharmacology was characterized with five peptide agonists (VIP, PACAP-27, PACAP-38, [Ala(11,22,28)]VIP, and R3P65). The rank order of potency (ROP) was consistent between assays for the individual receptor subtypes, however, higher agonist concentrations (approximately 100-fold) were required for stimulating [Ca2+]i when compared to [cAMP]i.
Dickson
Louise
L
Astellas CNS Research in Edinburgh, University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 45B, UK.
Aramori
Ichiro
I
Sharkey
John
J
Finlayson
Keith
K
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D002118:Calcium