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VIP and PACAP receptor pharmacology: a comparison of intracellular signaling pathways
Louise Dickson1, Ichiro Aramori, John Sharkey
1Astellas CNS Research in Edinburgh, University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 45B, UK.
Abstract:
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.
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