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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Barnes K, Turner AJ, Kenny AJ (1988) Electronmicroscopic immunocytochemistry of pig brain shows that endopeptidase-24.11 is localized in neuronal membranes. Neurosci Lett 94:64–69
Bowes MA, Kenny AJ (1986) Endopeptidase-24.11 in pig lymph nodes: purification and immuno-cytochemical identification in reticular cells. Biochem J 236:801–810
Brown G, Hogg N, Greaves M (1975) Candidate leukemia-specific antigen in man. Nature 258:454–456
Burstein Y, Buchner V, Pecht M, Trainin N (1988) Thymic humoral factor gamma2: purification and amino acid sequence of an immunoregulatory peptide from calf thymus. Biochemistry 27:4066–4071
Carrel S, De Tribolet N, Gross N (1982) Expression of HLA-DR and common acute lymphoblastic leukemia antigens on glioma cells. Eur J Immunol 23:354–357
Carrel S, Schmidt-Kessen A, Mach J-P, Heumann D, Girardet C (1983) Expression of common acute lymphoblastic leukemia antigen (CALLA) on human malignant melanoma cell lines. J Immunol 130:2456–2466
Coletti-Previero MA, Mattras H, Descomps B, Previero A (1981) Purification and substrate characterization of a human enkephalin-degrading aminopeptidase. Biochem Biophys Acta 657:122–127
Cooper MD, Mulvaney D, Continho A, Cazenave P (1986) A novel cell surface molecule on early B-lineage cells. Nature 321:616–618
Danielsen AM, Noren O, Sjostrom H, Ingram J, Kenny AJ (1980) Aspartate aminopeptidase: purification by immunoadsorbent chromatography and properties of the detergent and proteinasesolubilized forms. Biochem J 189:591–603
Devault A, Lazure C, Nault C, LeMoual H, Seidah NG, Chretien M, Kahn P, Powell J, Mallet J, Beaumont A, Roques BP, Crine P, Boileau G (1987) Amino acid sequence of rabbit kidney neutral endopeptidase 24.11 (enkephalinase) deduced from a complementary DNA. EMBO J 6:1317–1322
Dupont A, Cusan L, Garon M, Alvarado-Urbina G, Labrie F (1977) Extremely rapid degradation of [3H]-methionine-enkephalin by various rat tissues in vivo and in vitro. Life Sci 21:907–914
Erdös EG, Wagner B, Harburg CB, Painter RG, Skidgel RA, Fa X (1989) Down-regulation and inactivation of neutral endopeptidase 24.11 (enkephalinase) in human neutrophils. J Biol Chem 264:14519–14523
Fischer EG, Falke NE (1987) Interaction of met-enkephalin with human granulocytes. Ann NY Acad Sci 496:146–150
Flentke GR, Munoz E, Huber BT, Plant AG, Kettner CA, Bachovchin WW (1991) Inhibition of dipeptidylaminopeptidase IV (DP-IV) by Xoa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T cell formation. Proc Natl Acad Sci USA 88:1556–1559
Fulcher IS, Pappin DJC, Kenny AJ (1986) The N-terminal amino acid sequence of pig kidney endopeptidase-24.11 shows homology with pro-sucrase-isomaltase. Biochem J 240:305–308
Funkhouser JD, Tangada SD, Jones M, O SJ, Peterson DA (1991) p146 type II alveolar epithelial cell antigen is identical to aminopeptidase N. Am J Physiol 260:274–279
Gee NS, Bowes MA, Buck P, Kenny AJ (1985) An immunoradiometric assay for endopeptidase-24.11 shows it to be a widely distributed enzyme in pig tissues. Biochem J 228:119–126
Greaves MF, Brown G, Rapson N, Lister TA (1975) Antisera to acute lymphoblastic leukemia cells. Clin Immunol Immunopathol 4:67–72
Greaves MF, Haiti G, Newman RA, Sutherland DR, Ritter MA, Ritz J (1983) Selective expression of the common acute lymphoblastic leukemia (gp100) antigen on immature lymphoid cells and their malignant counterparts. Blood 61:628–639
Hambrook JM, Morgan BA, Rance MJ, Smith CFC (1976) Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature 262:782–783
Hersh LB, Morihara K (1986) Comparison of the subsite specificity of the mammalian neutral endopeptidase-24.11 (enkephalinase) to the bacterial neutral endopeptidase thermolysin. J Biol Chem 261:6433–6437
Hioki Y, Okada K, Ito H, Matsuyama K, Yano M (1991) Endothelin converting enzyme of bovine carotid artery smooth muscle cells. Biochem Biophys Res Commun 174:446–451
Hussain MM, Tranum-Jensen J, Noren O, Sjostrom H, Christiansen K (1981) Reconstitution of purified amphiphilic pig intestinal microvillus aminopeptidase. Biochem J 199:179–186
Indig FE, Pecht M, Trainin N, Burstein Y, Blumberg S (1991) Hydrolysis of thymic humoral factor gamma 2 by neutral endopeptidase EC 3.4.24.11 Biochem J 278:891–894
Isaac RE (1988) Neuropeptide-degrading endopeptidase activity of locust (Schistocerca gregaria) synaptic membranes. Biochem J 255:843–847
Jongeneel CV, Bouvier J, Bairoch A (1989) A unique signature identifies a family of zinc-dependent metallopeptidases. FEBS Lett 242:211–214
Kenny AL, Turner AJ (eds) (1987) Mammalian ectoenzymes, Elsevier, Amsterdam
Kenny AJ, Stephenson SL, Turner AJ (1987) Cell-surface peptidases. In: Kenny AJ, Turner AJ (eds) Mammalian ectoenzymes. Elsevier, Amsterdam, pp 169–210
Kerr MA, Kenny AJ (1974) The purification and specificities of a neutral endopeptidase from rabbit kidney brush border. Biochem J 137:477–488
Kreil G, Haiml L, Suchanek G (1980) Stepwise cleavage of the pro part of promelittin by dipeptidyl peptidase IV. Evidence for a new type type of precursor-product conversion. Eur J Biochem 111:49–58
Lalu K, Lameplo S, Nummelin-Kortelainen M, Vanha-Perttula T (1984) Purification and partial characterization of aminopeptidase A from the serum of pregnant and non-pregnant women, Biochim Biophys Acta 789:324–333
Lane A, Rance Mi, Walter DS (1977) Subcellular localization of leucine-enkephalin hydrolyzing activity in rat brain. Nature 269:75–76
LeTarte M, Vera S, Tran R, Addis JB, Omizuka RJ, Quackenbush EJ, Jongeneel CV, McInnes RR (1988) Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med 168:1247–1253
Leung MK (1990) Degradation of opioid peptides in invertebrate hemolymph. International workshop on developmental and comparative neuroimmunology, abstract no 12
Leung MK, Le SX (1991) Enkephalin degradative enzymes in serum and hemolymph: a comparative study. Adv. Neuroimmunol 1:17–26
Leung MK, Lundy J (1990) Opioid neuropeptides in invertebrate haemolymph. In: Forey E, Stefano GB (eds) Comparative aspects of neuropeptides. Manchester University Press, Manchester, pp 516–517
Look AT, Ashmun RA, Shapiro LH, Peiper SE (1989) Human myeloid plasma membrane glycoprotein CD13 (gp150) is identical to aminopeptidase. N. J Clin Invest 83:1299–1307
Lygren J, Revhaug PG, Burhol KE, Giercksky KE, Jenssen TG (1984) Vasoactive intestinal peptide and somatostatin in leukocytes. Scand J Clin Lab Invest 44:347–351
Malfroy B, Swertz JB, Guyon A, Roques BP, Schwartz JC (1978) High affinity enkephalin-degrading peptidase in brain is increased after morphine. Nature 276:523–526
Malfroy B, Schofield P, Kuang WJ, Seeburg PH, Mason AJ, Henzel WJ (1987) Molecular cloning and amino acid sequence of rat enkephalinase. Biochem Biophys Res Commun 144:59–66
Malfroy B, Kuang WJ, Seeburg PH, Mason AJ, Schofield PR (1988) Molecular cloning and amino acid sequence of human enkephalinase (neutral endopeptidase). FEBS Lett 229:206–210
Marini M, Roscetti G, Bongiorno L, Urbani A, Roda LG (1990) Hydrolysis and protection. from hydrolysis of enkephalins in human plasma. Neurochem Res 15:61–67
Massoulie J, Bon S (1982) The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Annu Rev Neurosci 5:57–106
Matsas R, Fulcher IS, Kenny AJ, Turner Ai (1983) Substance P and [Leu] enkephalin are hydrolyzed by an enzyme in pig caudate membranes that is identical with the endopeptidase of kidney microvilli. Proc Natl Acad Sci USA 80:3111–3115
Matsas R, Kenny J, Turner All (1984) The metabolism of neuropeptides: the hydrolysis of peptides, including enkephalins, tachykinins and their analogues by endopeptidase-24.11. Biochem J 223:433–440
Matsas R, Stephenson SL, Hryszko J, Kenny AJ, Turner AJ (1985) The metabolism of neuropeptides: phase-separation of synaptic membrane preparations with Triton X-114 reveals the presence of aminopeptidase N. Biochem J 231:445–449
Matsas R, Kenny AJ, Turner AJ (1986) An immunohistochemical study of endopeptidase-24.11 (`enkephalinase’) in the pig nervous system. Neuroscience 18:991–1012
Medeiros MS, Balmforth AJ, Vaughan PFT, Turner AJ (1991) Hydrolysis of atrial and brain natriuretic peptides by the human astrocytoma clone D384 and the neuroblastoma line SH-SYSY. Neuroendocrinology 54:295–302
Meglitsch PA (1967) In: Invertebrate zoology. Oxford University Press, New York
Painter RG, Dukes R, Sullivan J, Carter R, Erdös EG, Johnson AR (1988) Function of neutral endopeptidase on the cell membrane of human neutrophils. J. Biol Chem 263:9456–9461
Peirart ME, Najdovski T, Appelboom TE, Deschodt-Lanckmann MM (1988) Effect of human endopeptidase-24.11 (“enkephalinase”) on IL-1-induced thymocyte proliferation activity. J Immunol 140:3808–3811
Poole S, Bird TA, Selkirk S, Gaines-Das RE, Choudry Y, Stephenson SL, Kenny AJ, Saklatvala J (1990) Fate of injected interleukin-1 in rats: sequestration and degradation in kidney. Cytokine 2:416–422
Raftery MA, Hunkapillar MW, Strader CD, Hood LE (1980) Acetylcholine receptor: complex of homologous subunits. Science 208:1454–1457
Ritz J, Pesando JM, Notis-McConarty J, Lazarus H, Schlossman SF (1980) A monoclonal antibody to human acute lymphoblastic leukemia antigen. Nature 283:583–585
Roques BP, Beaumont A (1990) Neutral endopeptidase-24.11 inhibitors: from analgesics to antihypertensives. Trends Pharmacol Sci 11: 245–249
Scholz W, Mentlein R, Heymann E, Feller AC, Flad HD (1985) Interleukin-2 production by human T lymphocytes identified by antibodies to dipeptidyl peptidase IV. Cell Immunol 89:11–19
Schon E, Mansfeld HW, Demuth HU, Barth A, Ansorge S (1985) The dipeptidyl peptidase IV, a membrane enzyme involved in the proliferation of T lymphocytes. Biomed Biochim Acta 44:K9–K15
Shipp MA, Richardson NE, Sayre PH, Brown NR, Masteller EL, Clayton LK, Ritz J, Reinherz EL (1988) Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci USA 85:4819–4823
Shipp MA, Vijayaraghavan J, Schmidt EV, Masteller EL, D’Adamio L, Hersh LB, Reinherz EL (1989) Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 (“enkephalinase”):direct evidence by cDNA transfection analysis. Proc Natl Acad Sci USA 86:297–301
Shipp MA, Stefano GB, D’Adamio L, Switzer SN, Howard FD, Sinisterra J, Scharrer B, Reinherz EL (1990) Down-regulation of enkephalin mediated inflammatory responses by CD10/neutral endopeptidase 24.11. Nature 347:394–396
Smith EM, Blalock JE (1981) Human lymphocyte production of ACTH and endorphin-like substances: associated with leukocyte interferon. Proc Natl Acad Sci USA 78:7530–7534
Stefano GB, Leung MK, Zhao X, Scharrer B (1989a) Evidence for the involvement of opioid neuropeptides in the adherence and migration of immunocompetent invertebrate hemocytes. Proc Natl Acad Sci USA 86:626–630
Stefano GB, Cadet P, Scharrer B (1989b) Stimulatory effects of opioid neuropeptides on locomotory activity and conformational changes in invertebrate and human immunocytes: evidence for a subtype of opioid receptor. Proc Natl Acad Sci USA 86:6307–6311
Stefano GB, Shipp MA, Scharrer B (1991) A possible immunoregulatory function for Metenkephalin-Arg6-Phe7 involving human and invertebrate granulocytes. J Neuroimmunol 31: 97–103
Stephenson SL, Kenny AJ (1987) The hydrolysis of human atrial natriuretic peptide by pig kidney microvillar membranes is initiated by endopeptidase-24.11. Biochem J 243:183–187
Thorsett ED, Wyvratt MJ (1987) Inhibition of zinc peptidases that hydrolyse neuropeptides. In: Turner AJ (ed) Neuropeptides and their peptidases. VCH, New York, pp 229–292
Tredosiewicz LK, Malizia G, Oakes J, Losowsky M, Janossy G (1985) Expression of the common acute lymphoblastic leukemia antigen (CALLA, gp100) in the brush border of normal jejunum and jejunum of patients with coeliac disease. J Clin Pathol 38:1002–1006
Turner AJ (ed) (1987) Neuropeptides and their peptidases. Ellis Horwood, Chichester
Turner AJ, Dowdall MJ (1984) The metabolism of neuropeptides: both phosphoramidon-sensitive and captopril—sensitive metallopeptidases are present in the electric organ of Torpedo marmorata. Biochem J 222:255–259
Turner AJ, Matsas R, Kenny AJ (1985) Are there neuropeptide-specific peptidases? Biochem Pharmacol 34:1347–1356
Turner AJ, Hooper NM, Kenny AJ (1987) Neuropeptide metabolism. In: Kenny AJ, Turner AJ (eds) Mammalian ectoenzymes. Elsevier, Amsterdam, 211–248
Ulmer AJ, Matter T, Feller AC, Heymann E, Flad H–D (1989) T1119–4–7 and 4EL1C7 but not B1.19.2 (all clustered in CDw26) bind to dipeptidyl peptidase IV (DPP–IV). 7th international congress of immunology. Fisher, Stuttgart, p 151 (abstract)
Van Epps DE, Kutvirt SJ (1987) Modulation of human neutrophil adherence by ß-endorphin and Met-enkephalin. J Neuroimmunol 15:219–228
Van Epps DE, Saland L (1984) ß-endorphin and Met-enkephalin stimulate human peripheral blood mononuclear cell chemotaxis. J Immunol 132:3046–3053
Venturelli F, Roscetti G, Posssenti R, Vita F, Roda LG (1985) Peripheral enkephalin hydrolysis in different animal species: a comparative study. Neurochem Res 10:333–342
Vogel Z, Altstein M (1979) The effect of puromycin on the biological activity of Leu-enkephalin. FEBS Lett 98:44–47
Vogt-Schaden M, Ciagelmann M, Hock D, Herbst F, Forssmann WG (1989) Degradation of porcine brain natriuretic peptide (pBNP-26) by endoprotease-24.11 from kidney cortical membranes. Biochem biophys Res Commun 161:1177–1183
Welch PA, Burrows PD, Gillis S, Cooper MD (1990) J Cell Biochem [Suppl] 14D:267 (abstract)
Wilk S (1986) Neuropeptide-specific peptidases: does brain contain a specific TRH-degrading enzyme? Life Sci 39:1487–1492
Wu Q, Tidmarsh GF, Welch PA, Pierce JH, Weissman IL, Cooper MD (1989) The early B lineage antigen BP-1 and the transformation-associated antigen 6C3 are on the same molecule. J Immunol 143:3303–3308
Wu Q, Lahti JM, Air GM, Burrows PD, Cooper MD (1990) Molecular cloning of the murine BP-1/6C3 antigen: a member of the zinc-dependent metallopeptidase family. Proc Natl Acad Sci USA 87:993–997
Wu Q, Li L, Cooper MD, Pierres M, Gorvel JP (1991) Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3. Proc Natl Acad Sci USA 88:676–680
Yamada R, Mizutani S, Kuranchi O, Okono K, Imaizumi H, Narita O, Tomoda Y (1988) Purification and characterization of human placental aminopeptidase A. Enzyme 40:223–230
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1994 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Turner, A.J., Leung, M.K., Stefano, G.B. (1994). Degradation of Neuropeptide Signal Molecules in Immunocytes of Vertebrates and Invertebrates. In: Scharrer, B., Smith, E.M., Stefano, G.B. (eds) Neuropeptides and Immunoregulation. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78480-4_10
Download citation
DOI: https://doi.org/10.1007/978-3-642-78480-4_10
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-78482-8
Online ISBN: 978-3-642-78480-4
eBook Packages: Springer Book Archive