Degradation of Neuropeptide Signal Molecules in Immunocytes of Vertebrates and Invertebrates

Abstract

There are now substantial grounds for believing that the enkephalins have multiple physiological roles and can serve as neurotransmitters, neurohormones, or neuromodulators as well as immunomodulators. Other neuropeptides also function as signaling molecules in both the nervous and immune systems. It is therefore important to establish the mechanism by which the peptide signal is terminated. Previous studies (see, for example Turner et al. 1987) have ruled out a presynaptic uptake mechanism for neuropeptides in general. It has been demonstrated that if enkephalin is added to neural tissues or blood, it is rapidly metabolized (Lane et al. 1977; Vogel and Altstein 1979). This fact alone does not demonstrate the presence of a specific “enkephalinase.” Indeed, a nonspecific enzyme may serve equally well since specificity may be achieved by the location of the enzyme and the presence of only enkephalinergic signal molecules. The consensus of opinion now is that specific “neuropeptidases” do not exist, but rather that a handful of enzymes located at the cell surface of many different cell types can act in concert to degrade regulatory peptides. To date there is only one exception to this general rule: pyroglutamyl aminopeptidase II (EC 3.4.19.-), a metalloenzyme which appears to be a specific degrading enzyme for thyrotropinreleasing hormone (Wilk 1986). Much of our understanding of neuropeptide metabolism has come from a study of the peptidases of the mammalian renal brush-border membrane.