Specific binding of vasoactive intestinal peptide to human circulating mononuclear cells

Abstract

The interaction of the neuropeptide vasoactive intestinal peptide with human circulating mononuclear cells has been studied. Mononuclear cells were able to bind radiolabelled vasoactive intestinal peptide; the binding was rapid, reversible, saturable, and specific for vasoactive intestinal peptide. A fragment of vasoactive intestinal peptide (10–28) was 25-fold less effective than intact peptide as a competitor for the binding of the tracer. Secretin was 100-fold less effective as a competitor and glucagon competed poorly even at concentrations 10 000 times greater than that of the tracer molecule. In tracer dilution studies, the binding suggested a single class of binding sites with an apparent dissociation constant (Kd) of 2.4 × 10−10 M and a capacity of 2 000 sites per cell. In the presence of vasoactive intestinal peptide, there was a dose-dependent augmentation of cyclic AMP in the mononuclear cells. The concentration of vasoactive intestinal peptide which produced a half-maximal effect was the same as the Kd for the peptide binding. We conclude that mononuclear cells have specific high-affinity binding sites for vasoactive intestinal peptide. Interactions between mononuclear cells and vasoactive intestinal peptide may be an important mechanism modulating local immune responses within tissues innervated by vasoactive intestinal peptide containing neurons.