scholarly journals Kidney neutral endopeptidase and the hydrolysis of enkephalin by synaptic membranes show similar sensitivity to inhibitors

1982 ◽  
Vol 203 (2) ◽  
pp. 519-522 ◽  
Author(s):  
I S Fulcher ◽  
R Matsas ◽  
A J Turner ◽  
A J Kenny
Keyword(s):  
Neutral Endopeptidase ◽  
Synaptic Membranes ◽  
General Role ◽  
Leucine Enkephalin ◽  
Pig Kidney ◽  
Pig Brain ◽  
Endopeptidase Activity ◽  
Hydrolysis Of

Neutral endopeptidase (EC 3.4.24.11) from pig kidney hydrolyses [125I]iodo-insulin B-chain and leucine-enkephalin. Both activities were equally sensitive to inhibition by phosphoramidon [N-(alpha-L-rhamnopyranosyloxyhydroxyphosphinyl)-L-leucyl-L-tryptophan] and thiorphan [N-(DL-2-benzyl-3-mercaptopropionyl)glycine]. Thermolysin hydrolysis of insulin B-chain was also sensitive to both inhibitors. The hydrolysis of the Gly3-Phe4 bond of Leu-enkephalin by synaptic membranes prepared from pig brain was partially inhibited by phosphoramidon and thiorphan. Synaptic membranes appear to contain another endopeptidase activity that is insensitive to these reagents. These observations suggest that enzymes similar to the kidney endopeptidase may play a general role in neuropeptide metabolism.

scholarly journals The metabolism of neuropeptides. Neurokinin A (substance K) is a substrate for endopeptidase-24.11 but not for peptidyl dipeptidase A (angiotensin-converting enzyme)

1985 ◽  
Vol 231 (2) ◽  
pp. 357-361 ◽  
Author(s):  
N M Hooper ◽  
A J Kenny ◽  
A J Turner
Keyword(s):  
Substance P ◽  
Selective Inhibitor ◽  
Synaptic Membranes ◽  
Neurokinin A ◽  
Pig Kidney ◽  
Endopeptidase 24.11 ◽  
The Family ◽  
General Capacity ◽  
Substance K ◽  
Hydrolysis Of

Both endopeptidase-24.11 and peptidyl dipeptidase A have previously been shown to hydrolyse the neuropeptide substance P. The structurally related peptide neurokinin A is also shown to be hydrolysed by pig kidney endopeptidase-24.11. The identified products indicated hydrolysis at two sites, Ser5-Phe6 and Gly8-Leu9, consistent with the known specificity of the enzyme. The pattern of hydrolysis of neurokinin A by synaptic membranes prepared from pig striatum was similar to that observed with purified endopeptidase-24.11, and hydrolysis was substantially abolished by the selective inhibitor phosphoramidon. Peptidyl dipeptidase A purified from pig kidney was shown to hydrolyse substance P but not neurokinin A. It is concluded that endopeptidase-24.11 has the general capacity to hydrolyse and inactivate the family of tachykinin peptides, including substance P and neurokinin A.

scholarly journals The stimulation by transmitter substances and putative transmitter substances of the net activity of phospholipase A2 of synaptic membranes of cortex of guinea-pig brain

1975 ◽  
Vol 148 (2) ◽  
pp. 197-208 ◽  
Author(s):  
R J Gullis ◽  
C E Rowe
Keyword(s):  
Guinea Pig ◽  
Phospholipase A2 ◽  
Synaptic Vesicles ◽  
Optimum Concentration ◽  
Synaptic Membranes ◽  
Phospholipase A1 ◽  
Response Curves ◽  
Pig Brain ◽  
Hydrolysis Of ◽  
Guinea Pig Brain

1. The distribution of the hydrolyses of phosphatidylcholine by phospholipase A2 and phospholipase A1, and the hydrolysis of lysophosphatidylcholine by lysophospholipase, in subcellular and subsynaptosomal fractions of cerebral cortices of guinea-pig brain, was determined. 2. Noradrenaline stimulated hydrolysis by phospholipase A2 in whole synaptosomes, synaptic membranes and fractions containing synaptic vesicles. 3. Stimulation of hydrolysis by phospholipase A2 in synaptic membranes by noradrenaline was enhanced by CaCl2, and by a mixture of ATP and MgCl2. The optimum concentration of CaCl2, in the presence of ATP and MgCl2, for stimulation by 10 muM-noradrenaline was in the range 1-10muM. The optimum concentration for ATP-2MgCl2 in the presence of 1 muM-CaCl2 was in the range 0.1-1mM. 4. Hydrolysis by phospholipase A2 of synaptic membranes was also stimulated by acetylcholine, carbamoylcholine, 5-hydroxytryptamine, dopamine (3,4-dihydroxyphenethylamine), histamine, psi-aminobutyric acid, glutamic acid and aspartic acid. With appropriate concentrations of cofactors, sigmoidal dose-response curves were obtained, half-maximum stimulations being obtained with concentrations of stimulant in the range 0.1-1muM. 5. Taurine also stimulated hydrolysis of phosphatidylcholine by phospholipase A2. There were only slight stimulations with methylamine, ethylenediamine or spermidine. No stimulation was obtained with glucagon.

scholarly journals Purification of endopeptidase-24.11 (‘enkephalinase’) from pig brain by immunoadsorbent chromatography

1983 ◽  
Vol 215 (3) ◽  
pp. 519-523 ◽  
Author(s):  
J M Relton ◽  
N S Gee ◽  
R Matsas ◽  
A J Turner ◽  
A J Kenny
Keyword(s):  
Monoclonal Antibody ◽  
Amino Acid ◽  
Deae Cellulose ◽  
Single Step ◽  
Endopeptidase 24.11 ◽  
Pig Brain ◽  
Endopeptidase Activity ◽  
Hydrolysis Of ◽  
The Brain ◽  
Subunit Size

Membrane preparations from striatum of pig brain contain endopeptidase activity towards iodoinsulin B-chain. Only 50% of the hydrolysis of insulin B-chain is inhibitable by phosphoramidon, and DEAE-cellulose chromatography can resolve the phosphoramidon-sensitive and -insensitive activities. The former activity (now designated ‘endopeptidase-24.11’) is responsible for hydrolysis of [D-Ala2,Leu5]enkephalin and is identical with an enzyme in brain that has previously been referred to as ‘enkephalinase’. Pig striatal endopeptidase-24.11 has now been purified to homogeneity in a single step by immunoadsorbent chromatography using a monoclonal antibody. The overall purification was 23 000-fold, with a yield of 30%. The brain enzyme appears to be identical with kidney endopeptidase-24.11 in amino acid composition as well as by immunological and kinetic criteria. However, it differs slightly in apparent subunit size (Mr = 87 000), attributable to differences in glycosylation.

scholarly journals The hydrolysis of endothelins by neutral endopeptidase 24.11 (enkephalinase).

1990 ◽  
Vol 265 (24) ◽  
pp. 14150-14155
Author(s):  
J. Vijayaraghavan ◽  
A.G. Scicli ◽  
O.A. Carretero ◽  
C. Slaughter ◽  
C. Moomaw ◽  
...  
Keyword(s):  
Neutral Endopeptidase ◽  
Endopeptidase 24.11 ◽  
Hydrolysis Of

Serum neutral endopeptidase activity in patients with primary biliary cirrhosis

1998 ◽  
Vol 114 ◽  
pp. A1258
Author(s):  
K. Horvát-Karajz ◽  
F. Szalay ◽  
P. Lakatos ◽  
L. Selmeci ◽  
A. Csepregi ◽  
...  
Keyword(s):  
Primary Biliary Cirrhosis ◽  
Neutral Endopeptidase ◽  
Biliary Cirrhosis ◽  
Endopeptidase Activity

scholarly journals Certain mouse strains are deficient in a kidney brush-border metallo-endopeptidase activity

1983 ◽  
Vol 209 (1) ◽  
pp. 251-255 ◽  
Author(s):  
J S Bond ◽  
J D Shannon ◽  
R J Beynon
Keyword(s):  
Brush Border ◽  
Inbred Mice ◽  
Neutral Endopeptidase ◽  
Renal Tissue ◽  
Mouse Strains ◽  
Ph Optimum ◽  
Brush Border Enzymes ◽  
Endogenous Inhibitors ◽  
Endopeptidase Activity ◽  
Proteinase A

Preparations of microvilli from kidneys of BALB/c mice contain an alkaline metallo-endopeptidase, meprin (metallo-endopeptidase from renal tissue). Certain genealogically related inbred mice are markedly deficient in meprin activity. The meprin-deficient strains (CBA/J and C3H/HeJ) exhibit normal levels of other brush-border enzymes: alkaline phosphatase, aminopeptidase M and another proteinase, a phosphoramidon-sensitive neutral endopeptidase. Meprin deficiency cannot be attributed to a shift in pH optimum and is unlikely to be due to the presence of endogenous inhibitors.

Transport of Leucine-Enkephalin Across the Blood-Brain Barrier in the Perfused Guinea Pig Brain

1987 ◽  
Vol 49 (1) ◽  
pp. 310-315 ◽  
Author(s):  
Berislav V. Zloković ◽  
Milo N. Lipovac ◽  
David J. Begley ◽  
Hugh Davson ◽  
Ljubiša Rakić
Keyword(s):  
Guinea Pig ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Leucine Enkephalin ◽  
Blood Brain ◽  
Pig Brain ◽  
Guinea Pig Brain

Influence of C-ANF receptor and neutral endopeptidase on pharmacokinetics of ANF in rats

1991 ◽  
Vol 260 (1) ◽  
pp. R208-R216 ◽  
Author(s):  
P. J. Chiu ◽  
G. Tetzloff ◽  
M. T. Romano ◽  
C. J. Foster ◽  
E. J. Sybertz
Keyword(s):  
High Performance ◽  
Fold Increase ◽  
Neutral Endopeptidase ◽  
Volume Of Distribution ◽  
Fourfold Increase ◽  
Control Value ◽  
Enzymatic Pathways ◽  
Hydrolysis Of

The role of C-atrial natriuretic factor (ANF) receptors and neutral endopeptidase (NEP) in the pharmacokinetics and hydrolysis of 125I-labeled ANF was evaluated in rats by using C-ANF and SCH 39370 to block the nonenzymatic and enzymatic pathways, respectively. After a bolus injection of 125I-ANF, the resulting area under the plasma concentration curve (AUC) with C-ANF treatment was seven times the control value with regard to trichloroacetic acid-precipitable (TCA-ppt) radioactivity (intact ANF). SCH 39370 tended to increase AUC, but the changes were not significant. Nevertheless, SCH 39370 suppressed the appearance of TCA-soluble radioactivity (hydrolytic products), indicating that in vivo inhibition of ANF degradation had occurred. SCH 39370 plus C-ANF produced a 15-fold increase in AUC for TCA-ppt radioactivity and a reduction in plasma TCA-soluble radioactivity. High-performance liquid chromatography (HPLC) analysis confirmed that combination treatment increased intact ANF and reduced hydrolytic products in the plasma. SCH 39370 reduced clearance (C) without altering volume of distribution in steady state (Vss) and half-life (t1/2). C-ANF decreased both C and Vss leading to a fourfold increase in t1/2, which was further prolonged by SCH 39370 (7.5 times control). Bilateral nephrectomy caused a proportionally similar decrease in Vss and C without changing t1/2, suggesting significant extrarenal metabolism of ANF. SCH 39370 systemically inhibits ANF hydrolysis; the resulting increase in ANF, however, is masked by the great capacity of ANF clearance receptors but can be revealed with excess C-ANF, suggesting that the plasma ANF concentrations are determined by the interplay of the C-ANF receptor and NEP systems.

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