Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists

Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.