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Identification and localization of a neprilysin-like activity that degrades tachykinin-related peptides in the brain of the cockroach, Leucophaea maderae, and locust, Locusta migratoria.

Neprilysin (NEP) is an endopeptidase, which has an important role in the inactivation of mammalian tachykinins. NEP-like activity has also been found in the brain of several insects; however, the lack of information about the cellular localization of this peptidase has hindered our understanding of its role in peptidergic signaling in insects. We now provide evidence that membrane-bound NEP is involved in the inactivation of tachykinin-related peptides in the brain of the cockroach, Leucophaea maderae, and the locust, Locusta migratoria. The L. maderae enzyme cleaved the cockroach peptide LemTRP-1 and the mammalian NEP substrate [DAla(2),Leu(5)]enkephalin at the Gly-Phe peptide bond. The enzyme was acted upon by the NEP inhibitors phosphoramidon (IC(50), 0.64 microM) and thiorphan (IC(50), 1.23 microM), and the detergent-solubilized enzyme had an Mr of approximately 300,000 and a neutral pH optimum. This endopeptidase cleaved another insect tachykinin-related peptide, CavTK-II, in a predictable manner at the Ala-Phe peptide bond, suggesting that the peptidase can hydrolyse tachykinin-related peptides with different structures. NEP activity was histochemically localized in several, but not all, regions of neuropil in the brain of L. maderae, including the central body, the lobula of the optic lobe, and the tritocerebrum. All of these regions are known to receive neuronal processes containing tachykinin-related peptides. A slightly different distribution pattern for NEP was observed in the brain of L. migratoria. Again, NEP was localized to regions of the neuropil that also display tachykinin-related peptide immunoreactivity. The data reported provide evidence for an evolutionary conserved role for NEP in the inactivation of tachykinin-related peptides in the brain.

Pubmed ID: 12541324 RIS Download

Mesh terms: Animals | Brain | Brain Chemistry | Cell Membrane | Chromatography, High Pressure Liquid | Cockroaches | Endopeptidases | Female | Grasshoppers | Hydrolysis | Insect Proteins | Male | Neprilysin | Peptidyl-Dipeptidase A | Tachykinins