Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminopeptidase M (EC 3.4.11.2), an enzyme present on the cell surface of vascular endothelium and/or smooth muscle, rapidly hydrolyzes leucyl- and arginyl-2-naphthylamides and a number of vasoactive peptides at physiologic pH. Utilizing both thin-layer chromatography and high pressure liquid chromatography, it was found that vascular aminopeptidase M converted kallidin to bradykinin and inactivated des(Asp1)angiotensin I, angiotensin III, hepta(5-11)substance P and hexa(6-11)substance P. Aminopeptidase M did not, however, hydrolyze bradykinin, angiotensin I, angiotensin II, saralasin, vasopressin, oxytocin or any form of substance P containing a component of the Arg-Pro-Lys-Pro sequence. Both the naphthylamidase and peptidase activities were inhibited similarly by known amino-peptidase M inhibitors including o-phenanthroline, amastatin, bestatin and puromycin. However, inhibitors of angiotensin I converting enzyme (captopril), carboxypeptidase N (MERGETPA), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme and dipeptidyl(amino)peptidase IV (diisopropylphosphofluoridate, DFP) were without effect. These results demonstrate that vascular, cell surface aminopeptidase M can selectively metabolize vasoactive peptides and may play a role in modulating their levels in the circulation and/or within the vessel wall.
 ...
PMID:Vascular, plasma membrane aminopeptidase M. Metabolism of vasoactive peptides. 240 81

Three types of cloned cDNA sequences for rat low molecular weight prekininogens were isolated and determined by molecular cloning and sequence analysis. The deduced amino acid sequences indicated that one, termed K-prekininogen, represents the counterpart of the known low molecular weight prekininogen present in other mammals, while the other two, called T-prekininogens, contain a novel T-kinin sequence which was recently identified from rat plasma. Although T- and K-prekininogens are highly homologous with each other, both of the T-prekininogens contain methionine, instead of arginine or lysine, as an amino acid preceding T-kinin and exhibit two consecutive amino acid deletions in the preceding region of T-kinin as compared with K-prekininogen. The former finding accounts for the previous observation of strong resistance of T-kininogens to cleavage with trypsin or kallikreins, while the latter finding has been explained by the structural analysis of genomic clones in which T-kinin-coding exon is contracted at its intron junction. A partial nucleotide sequence reported recently for the rat major acute phase protein (alpha 1-MAP) mRNA was found to be extremely related to the corresponding portion of the rat T-prekininogen mRNA. Furthermore, consistent with the previous report of the structural identity of major acute phase protein and alpha 1-cysteine proteinase inhibitor, kininogen closely resembles not only the former but also the latter in the amino acid compositions. The interrelationship among the triad of these proteins has been discussed.
 ...
PMID:Primary structures of the mRNAs encoding the rat precursors for bradykinin and T-kinin. Structural relationship of kininogens with major acute phase protein and alpha 1-cysteine proteinase inhibitor. 241 18

The rat major acute phase protein (alpha 1-MAP) is a cysteine protease inhibitor. The stoichiometry of the interaction between the inhibitor and enzyme was shown to be 1:2. A cDNA clone specific for rat alpha 1-MAP was isolated from a cDNA library prepared from an inflamed rat liver RNA template. The 1458-base pair insert was sequenced and positively identified by alignment with a partial amino acid sequence obtained by radiosequence analysis of the primary translation product for alpha 1-MAP. Complete sequence analysis determined the alpha 1-MAP cDNA coded for the entire protein with the exception of the first four amino acids of the signal peptide, all of which were identified by radiosequencing. The coding sequence spans 1282 nucleotides, followed by 115 base pairs of a 3' untranslated region. Two putative active sites, suggested by the enzyme-inhibitor ratio, have been identified by analysis of internal duplications of the alpha 1-MAP sequence and the alignment of these regions with the sequences of several low molecular weight cysteine protease inhibitors. A computer homology analysis of the protein sequence revealed a 59.3% overall identity between rat alpha 1-MAP and bovine low molecular weight (LMW) kininogen. The homology included the signal peptide regions. LMW kininogen is a precursor of bradykinin. alpha 1-MAP does contain a bradykinin sequence; the flanking amino acids are different, however. Evidence for the expression of the LMW and a high molecular weight kininogen from the same gene, and the high degree of homology between these proteins and the rat acute phase protein suggest that all three proteins belong to a precisely regulated gene family.
 ...
PMID:The relationship between rat major acute phase protein and the kininogens. 241 19

Two major acute phase alpha 1-protein (alpha 1-MAP, also called thiostatin) genes, one kininogen gene and one structurally related pseudogene, were isolated from a Buffalo rat genomic library and characterized. Comparison of the nucleotide sequence in the 5' proximal flanking region (1 kilobase) of a strongly inducible alpha 1-MAP gene with that in the non-inducible rat kininogen gene showed an overall homology of 90%, with a small number of randomly distributed base changes. In the intron downstream of the exon coding for Ile-Ser-bradykinin, the two alpha 1-MAP genes contained sequence sections similar to the section in the human kininogen gene which codes for the carboxyl-terminal chain of high molecular weight kininogen. Various features of the DNA related to gene expression such as initiation and termination sites of transcription, receptor binding sites, a Z-DNA section, and exon/intron splicing sites were identified. mRNAs expressed by alpha 1-MAP and kininogen genes in liver were studied by RNA blot hybridization using specific oligonucleotide probes. The kininogen gene expressed two mRNA species, one coding for high molecular weight kininogen, the other coding for low molecular weight kininogen. The levels of the two kininogen mRNAs in liver did not increase during acute inflammation. Only one type of mRNA, similar in size to low molecular weight kininogen RNA, was expressed by each of the two alpha 1-MAP genes. The levels of both alpha 1-MAP mRNAs increased strongly during acute inflammation.
 ...
PMID:Structure and expression of the genes for major acute phase alpha 1-protein (thiostatin) and kininogen in the rat. 243 9

The complete amino acid sequence of major acute phase alpha 1-protein of the rat (MAP) was derived from the nucleotide sequence of cloned cDNA. Amino acid analysis and partial sequencing supported the predicted sequence. The amino acid compositions of MAP and rat low-Mr kininogen are identical within experimental variation. The sequence is homologous (60%) to that of bovine low-Mr kininogen and both proteins carry the sequence for the vasoactive nonapeptide bradykinin in their C-terminal region. The rate of synthesis of MAP and the levels of MAP mRNA change coordinately during the acute phase response to inflammation.
 ...
PMID:Major acute phase alpha 1-protein of the rat is homologous to bovine kininogen and contains the sequence for bradykinin: its synthesis is regulated at the mRNA level. 257 92

Although kinins have been reported to affect cerebral vascular tone and permeability, their actions are not potentiated by angiotensin converting enzyme inhibitors. To investigate cerebral vascular kinin metabolism, porcine cerebral microvessels were isolated by differential sieving and centrifugation and characterized by microscopic examination and marker enzyme enrichment. Purified microvessels contained a membrane-bound carboxypeptidase which hydrolyzed the C-terminal Phe-Arg bond of both kallidin and bradykinin. Hydrolysis was optimal at pH 7.0, was activated more than 300% by 0.1 mM CoCl2, and was inhibited by o-phenanthroline and the carboxypeptidase N (EC 3.4.17.3) inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGETPA) (IC50 = 2 microM). Conversely, inhibitors of angiotensin I converting enzyme (captopril), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme (Z-Pro-prolinal), dipeptidyl(amino)peptidase IV (diprotin A) and amino-peptidase M (amastatin) had no effect. When the rates of C-terminal hydrolysis of kallidin by detergent-solubilized cerebral microvasculature were determined over a range of substrate concentrations (16.6 to 250 microM), the Km and Vmax values obtained were 26.0 +/- 3.0 microM and 14.7 +/- 1.3 nmol/min/ml (N = 4) respectively. These data suggest that a cerebral microvascular carboxypeptidase may play a role in vivo in modulating the effects of kinins on cerebral blood flow and permeability and in preventing circulating kinins from crossing the blood-brain barrier.
 ...
PMID:Kallidin and bradykinin metabolism by isolated cerebral microvessels. 339 72

A methionine aminopeptidase (MAP) found in rat liver microsomes behaves as membrane-bound enzyme. Triton-solubilized MAP when chromatographed on DEAE-cellulose columns was separated from other microsomal arylamidases. The enzyme hydrolyzes N-terminal methionine from methionyl-lysyl-bradykinin (Met-Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg) being then characterized as a typical aminopeptidase. It also shows preferential arylamidase activity upon Met-2-naphthylamide. MAP was activated by 2-mercaptoethanol and inhibited by p-hydroxymercuribenzoate. Contrarily to other well characterized aminopeptidases, MAP was not affected by EDTA, puromycin or bestatin. Altogether these data suggest that MAP is a unique microsomal enzyme distinct from other previously described aminopeptidases. It could be involved in the removal of methionine from nascent peptides during protein synthesis.
 ...
PMID:Microsomal methionine aminopeptidase: properties of the detergent-solubilized enzyme. 393 47

Bradykinin was infused intravenously and into the right renal artery of conscious rats that were chronically instrumented with catheters and miniaturized pulsed-Doppler flow probes. The effects on regional hemodynamics were compared with those in animals in which the infused kidney was denervated as well as in animals anesthetized with pentobarbital sodium. In intact rats bradykinin (1 microgram/min) caused an immediate increase in mean arterial blood pressure (MAP, 27 +/- 4 mmHg), heart rate (HR, 67 +/- 11 beats/min), mesenteric resistance (MR, 32 +/- 10%), and both right (RRR, 42 +/- 14%) and left renal resistance (LRR 21 +/- 8%). These effects were significantly different from those during intravenous infusion of the same dose of bradykinin (MAP, 6 +/- 3 mmHg; HR, 31 +/- 7 beats/min; MR, -21 +/- 5%; RRR, 8 +/- 4%; LRR, 6 +/- 3%). Pentobarbital greatly attenuated the responses to intrarenal bradykinin. In conscious animals denervation of the infused kidney completely abolished the cardiovascular effects of intrarenal bradykinin. In a separate group of animals, chlorisondamine (7.5 mg/kg iv) completely blocked the increases in MAP and HR during intrarenal bradykinin (1 microgram/min). It is concluded that selective renal administration of bradykinin alters afferent renal nerve activity and that this results in hemodynamic changes consistent with efferent sympathetic activation.
 ...
PMID:Activation of afferent renal nerves by intrarenal bradykinin in conscious rats. 615 Jun 45

1. The effects of intrathecal (i.t.) pretreatment with selective B1 or B2 kinin receptor antagonists were studied on the cardiovascular response to i.t. injection of bradykinin (BK) in conscious freely moving rats. 2. BK (81 pmol) produced an increase in mean arterial pressure (MAP: 9-13 mmHg) and decrease in heart rate (HR: 20-30 beats min-1) that reached a maximum 2 min after injection. 3. The BK-induced cardiovascular responses were dose-dependently and reversibly reduced by four antagonists with the following rank order of potency: Tyr, D-Arg[Hyp3,D-Phe7,Leu8]-BK = D-Arg[Tyr3,D-Phe7,Leu8]-BK = D- Arg[Hyp3,D-Phe7,Leu8]-BK > D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-BK (Hoe 140). These compounds failed to alter the cardiovascular response to i.t. injection of 8.1 nmol of substance P. 4. Other compounds acting on the B2 receptor, namely D-Arg[Hyp3,Gly6,Leu8]-BK, D-Arg[Hyp3,D-Phe7]-BK, D-Arg[Hyp2,Thi5,8,D-Phe7]-BK and D-Arg[Hyp3,Gly6,D-Phe7,Leu8]-BK or on the B1 receptor, [Leu8]-desArg9-BK, did not influence the cardiovascular responses to BK at doses devoid of intrinsic activity on MAP and HR. 5. None of the kinin receptor antagonists caused motor impairment, respiratory arrest or persisting cardiovascular changes. 6. These results confirm that the cardiovascular effects induced by i.t. BK are mediated by the activation of a B2 receptor in the rat spinal cord. However, the rank order of potency of antagonists does not conform to the classical B2 functional site characterized in peripheral tissues.
 ...
PMID:Cardiovascular effects of intrathecally administered bradykinin in the rat: characterization of receptors with antagonists. 750 24

Acute inflammation was induced in pigs using a single subcutaneous turpentine injection. The acute phase serum protein response was analyzed using crossed immunoelectrophoresis and immunodiffusion. The concentration of C reactive protein and haptoglobin increases 5-7 times 48 h after the injection, whereas the concentration of an alpha 2-globulin, named pig major acute phase protein (pig-MAP), increases at least 15-fold. A molecular mass of 115 kDa for pig-MAP was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This protein did not crossreact with antisera to human hemopexin, ceruloplasmin, H-kininogen and complement factor C3. Albumin and alpha-lipoprotein were negative acute phase proteins because their concentration significantly decreased during inflammation. Finally, the concentration of alpha 1-acid glycoprotein, fetuin, alpha 1-protease inhibitor, transferrin and alpha 2-macroglobulins, as well as total proteins, did not change significantly during inflammation.
 ...
PMID:Characterization of the acute phase serum protein response in pigs. 752 7


1 2 3 Next >>