VIP and PACAP Receptor Pharmacology:A Comparison of Intracellular Signaling Pathways

摘要

VIP/PACAP receptor activation stimulates the production of [cAMP]_i and [Ca~(2+)]i by coupling to independent G-protein sub-units, although agonist potencies for the different transduction pathways appear to differ. Using CHO-Kl cells stably expressing the human VIP/PACAP receptors (hVPAC_1R, hVPAC_2R, and hPAC_1R), functional assays ([cAMP]i and [Ca~(2+)]i) were established and the receptor pharmacology was characterized with five peptide agonists (VIP, PACAP27, 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 (～100-fold) were required for stimulating [Ca~(2+)]i when compared to [cAMP]i.