Characterization of vasoactive intestinal peptide receptors in human liver.

The stoichiometric, pharmacological and molecular properties of vasoactive intestinal peptide (VIP) receptors have been analyzed in human liver membranes and compared in parallel with those in rat liver membranes. The binding of [125I]VIP was rapid, saturable and specific. The stoichiometric data indicated the presence of two classes of binding sites in both human and rat liver membranes with Kd values of 0.22 (human) and 0.20 (rat) nM for the high-affinity site, and 27.3 (human) and 3.6 (rat) nM for the low-affinity site. Tracer binding was displaced by structurally related peptides with an order of potency: VIP = PACAP-27 > helodermin > secretin in human liver, and VIP = PACAP-27 = helodermin > secretin in rat liver. GTP inhibited [125I]VIP binding in a dose-dependent manner suggesting the involvement of a G protein in the signal transduction pathway. Cross-linking experiments revealed an apparent molecular mass for the VIP-receptor complex that was 67,500 +/- 2700 and 50,500 +/- 900 in human and rat preparations, respectively. VIP receptors were functional, since VIP stimulated adenylyl cyclase activity in a dose dependent manner with similar efficacy but different potency in human (ED50 = 1.2 nM) and rat (ED50 = 5.8 nM) liver membranes.