High affinity displacement of [H-3]NPY binding to the crude venom of Conusanemone by insect neuropeptides

The venom from Conus anemone contains a protein, named ANPY toxin, which di splayed high affinity (IC50 in nanomolar range) to neuropeptide Y (NPY), [L eu(31), Pro(34)]NPY, peptide YY, pancreatic polypeptide, the Y-1 antagonist 1229U91, and C-terminal NPY fragments. N-terminal fragments and the free a cid form of NPY did not bind to ANPY. The truncated NPY fragments displayed very low affinity to Y-1 receptors and partially inhibited [H-3]NPY bindin g to anti-NPY antiserum. Several insect neuropeptides, the sequences of whi ch related to the C-terminal fragments of NPY, were observed to bind with s imilar affinity or even 20 times higher (Lom-MS and Scg-NPF) affinity than NPY. In contrast, no significant binding of these insect peptides was obser ved for Y-1 receptors and anti-NPY antiserum. Therefore, ANPY can be viewed as an acceptor that binds with very high affinity to a broad spectrum of v ertebrate and invertebrate neuropeptides that share a similar C-terminal am ino acid sequence. (C) 1999 Academic Press.