Metabolism of Tachykinins by Cell-Surface Peptidases

Tachykinins are rapidly metabolised by tissue preparations and their inactivation is believed to occur through hydrolysis by cell-surface ecto-peptidases [1]. Enzymic and immunocytochemical studies in our laboratory have previously implicated endopeptidase-24.11 (‘ enkephalinase’, EC 3.4.24.11) in the metabolism of substance P [2–4]. The ability of pig striatal synaptic membranes to hydrolyse substance P was abolished by phosphoramidon and by an antiserum to the endopeptidase [2]. Furthermore, substance P was the best substrate identified for the enzyme in vitro [3]. We have also been able to demonstrate immunohistochemically the co-localisation of endopeptidase and substance P in specific brain regions, including globus pallidus and nucleus interpeduncular is [4]. More recently, neurokinins A and B have also been shown to be good substrates for endopeptidase-24.11, implicating this enzyme in their metabolism [5,6].