MEMBRANE PEPTIDASES OF THE NERVOUS AND IMMUNE-SYSTEMS

The plasma membrane of many cell-types contains a battery of peptidases that serve to modulate or terminate the action of regulatory peptides. The majority of these are zinc metallopeptidases and these enzymes are especially abundant in the brush border membranes of renal and intestinal microvilli. It is, however, in the nervous system that they have been most intensively studied with regard to their physiological roles. In higher primates the major plasma membrane endopeptidase is endopeptidase-24.11 (neutral endopeptidase, E-24.11, EC 3.4.24.11) which is the key enzyme initiating the hydrolysis of opioid peptides, tachykinins and atrial natriuretic peptides. This endopeptidase may act in concert with several aminopeptidases as well as peptidyl dipeptidase A (angiotensin converting enzyme, EC 3.4.15.1) to complete the degradation of synaptically released neuropeptides, terminating their physiological actions. Molecular cloning of several of these membrane peptidases has revealed their identity with surface antigens of cells of the immune system (cluster differentiation or CD antigens). Their precise functions remain unclear although it is likely that they process immunoregulatory peptides, thereby playing a role in cellular signalling in the immune system. The occurrence of opioid and other neuropeptides in the immune system lends weight to this concept.