Neuropeptide Metabolism: Properties of an Endopeptidase from Heads of Drosophila Melanogaster

Abstract

The hydrolysis of neuropeptides by ectoenzymes positioned on the surface of plasma membranes is now recognised to be an important step in the inactivation of many peptide messengers (Turner et al. 1987). In vertebrates relatively few membrane-bound enzymes are responsible for the metabolism of a wide range of neuropeptide transmitters and hormones, in a variety of tissues. For example, endopeptidase-24:11, an enzyme that appears to have a general role in the metabolism of a number of mammalian neuropeptides and can initiate the breakdown of peptides with blocked N- and C- termini and internal hydro-phobic residue (Turner, 1987). Recently, we have shown that a similar enzyme is present in membranes prepared from nervous tissue, fat-body, hindgut and Malpighian tubules of the locust, Schistocerca gregaria and is enriched in a synaptic membrane preparation (Isaac, 1988). The enzyme can initiate the hydrolysis of the blocked peptide AKH I by cleaving the Asn-Phe bond. Although the substrate specificity of this enzyme has not yet been defined, it may have an important role in the metabolism of many insect peptides possessing an internal phenylalanine residue. In the present paper we report the occurrence of a similar endopeptidase in membranes prepared from the heads of Drosophila melanogaster. Our considerable knowledge of the genetics of D. melanogaster make this insect a particularly convenient model for the molecular analysis of neuropeptide action.