High Affinity Displacement of [3H]NPY Binding to the Crude Venom of Conus anemone by Insect Neuropeptides

Abstract

The venom from Conus anemone contains a protein, named ANPY toxin, which displayed high affinity (IC50 in nanomolar range) to neuropeptide Y (NPY), [Leu31, Pro34]NPY, peptide YY, pancreatic polypeptide, the Y1 antagonist 1229U91, and C-terminal NPY fragments. N-terminal fragments and the free acid form of NPY did not bind to ANPY. The truncated NPY fragments displayed very low affinity to Y1 receptors and partially inhibited [3H]NPY binding to anti-NPY antiserum. Several insect neuropeptides, the sequences of which related to the C-terminal fragments of NPY, were observed to bind with similar affinity or even 20 times higher (Lom-MS and Scg-NPF) affinity than NPY. In contrast, no significant binding of these insect peptides was observed for Y1 receptors and anti-NPY antiserum. Therefore, ANPY can be viewed as an acceptor that binds with very high affinity to a broad spectrum of vertebrate and invertebrate neuropeptides that share a similar C-terminal amino acid sequence.