Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 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

Vasoactive peptides contain a high proportion of proline residues which make them resistant to hydrolysis by many peptidases. However, post proline cleaving enzyme (PPCE; EC 3.4.21.26), a proline specific endopeptidase which specifically hydrolyzes internal peptide bonds on the carboxyl side of proline residues, has been shown to inactivate numerous vasoactive peptides including angiotensins, kinins, substance P, vasopressin and oxytocin. In order to determine whether PPCE could be involved in vascular metabolism of vasoactive peptides, we carried out localization and characterization studies of PPCE-like activity in hog aorta and mesenteric artery. PPCE was assayed fluorometrically at pH 7.0 using the specific PPCE substrate CBZ-Gly-Pro-4-methyl-coumarinylamide. The subcellular distribution of vascular PPCE was essentially the same as that of the cytosolic marker enzyme lactic dehydrogenase (LDH). PPCE was enriched six-fold in the cytosolic fraction (11.4 +/- 2.7 units/mg) and unlike the plasma membrane-bound proline specific exopeptidase dipeptidyl-(amino)peptidase IV (DAP IV; EC 3.4.14.5), little or no activity could be detected in the microsomal or plasma membrane fractions. Similar to PPCE characterized from other sites, vascular PPCE was stabilized and activated by dithiothreitol and EDTA, and inhibited by DFP, p-chloromercuriphenyl sulfonic acid, L-1-tosylamido-2-phenylethylchloromethyl ketone, Cu++, Ca++, and Zn++. Vascular PPCE was unaffected by inhibitors of trypsin and kallikrein (Aprotinin, ABTI), aminopeptidase M (bestatin, amastatin), neutral endopeptidase (phosphoramidon), angiotensin I converting enzyme (captopril) or carboxypeptidase N (MERGETPA). These data demonstrate that PPCE is present in vascular endothelium and/or smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Vascular, post proline cleaving enzyme: metabolism of vasoactive peptides. 354 18

A 59-year-old man was admitted to our hospital because of fever in August 1991. Bone marrow showed normocellularity with 41.5% of CD13, 14, 33 positive blasts, and a diagnosis of AMMoL was made. Laboratory investigation revealed hyponatremia and elevated serum ADH level, indicating the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Intensive chemotherapy successfully induced hematological complete remission and his serum sodium level became normal. In February 1992, he developed proteinuria and findings were consistent with nephrotic syndrome (NS). Renal biopsy specimen showed membranous proliferative glomerulonephritis and massive infiltration of macrophages, and his serum interleukin 6 level was elevated. Five months later, he suffered from pancytopenia and elevation of biliary enzymes with increase of hemophagocytic histiocytes in his bone marrow (hemophagocytic syndrome). He transiently responded to low dose chemotherapy but he died due to severe infection. It is interesting that association between macrophages and/or cytokines with these various complications was suggested in AMMoL.
 ...
PMID:[Acute myelomonocytic leukemia complicated with syndrome of inappropriate secretion of antidiuretic hormone, nephrotic syndrome, and hemophagocytic syndrome]. 756 94

Normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) received aminopeptidase M (AmM) delivered into the paraventricular nucleus of the hypothalamus (PVN). Resulting changes in blood pressure were recorded in both anesthetized and alert animals. The findings indicate significant dose-determined decreases in blood pressure in members of both strains with SHR more responsive than WKY rats. The respective drops in blood pressure for members within each strain were equivalent for the anesthetized and alert conditions. Pretreatment with the specific angiotensin receptor antagonist, sarthran, [Sar1, Thr2] Angll, into the PVN greatly diminished these responses, suggesting the involvement of the brain angiotensin system. Additionally, a sympathetic nervous system blocker, hexamethonium, and the arginine vasopressin antagonist, Pmp1, O-Me-Tyr2-[Arg] vasopressin, were peripherally administered to assess the potential contributions of these systems to cardiovascular regulation by the brain angiotensin system. The use of these blockers, individually and combined, attenuated responsiveness to infusion of AmM into the PVN. We conclude that AmM can act as a hypotensive agent in both SHR and WKY rats, and that this decrease in blood pressure is at least partially mediated via the brain angiotensin system although other systems may play a role.
 ...
PMID:Microinfusion of aminopeptidase M into the paraventricular nucleus of the hypothalamus in normotensive and hypertensive rats. 896 89

Given that the existence of a local renin-angiotensin system (RAS) in the pituitary and its participation in the regulation of blood pressure and other biological functions are widely accepted, the aim of this work is to analyze the influence of dietary cholesterol on the activity of the enzymes involved in the metabolism of the effector peptides of the renin-angiotensin system (angiotensin II and III) and vasopressin, in the pituitary of male and female mice fed on a cholesterol-enriched diet (1% cholesterol and 0.5% cholic acid). Soluble and membrane-bound pituitary aminopeptidase A (aspartyl- and glutamyl-aminopeptidase), aminopeptidase M (alanyl-aminopeptidase), aminopeptidase B (arginyl-aminopeptidase) and cystinyl-aminopeptidase activities were fluorimetrically measured. In female mice, cholesterol-enriched diet produced a significant increase in soluble aspartyl- and membrane-bound aspartyl- and glutamyl-aminopeptidase activities, and a significant decrease in membrane-bound alanyl-, arginyl- and cystinyl-aminopeptidase activities. In male mice, after feeding the diet, a significant increase in soluble glutamyl- and membrane-bound arginyl-aminopeptidase activities was observed. Our results indicate differential effects of dietary cholesterol on the metabolism of angiotensin II and III and vasopressin in the pituitary of male and female mice.
 ...
PMID:Pituitary aminopeptidase activities involved in blood-pressure regulation are modified by dietary cholesterol: sex differences. 1173 Sep 80

Aminopeptidase N (APN)/CD13 (EC 3.4.11.2) is a transmembrane protease present in a wide variety of human tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). APN/CD13 expression is dysregulated in inflammatory diseases and in cancers (solid and hematologic tumors). APN/CD13 serves as a receptor for coronaviruses. Natural and synthetic inhibitors of APN activity have been characterized. These inhibitors have revealed that APN is able to modulate bioactive peptide responses (pain management, vasopressin release) and to influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis). Therefore, inhibition of APN/CD13 may lead to the development of anti-cancer and anti-inflammatory drugs. This review provides an update on the biological and pharmacological profiles of known natural and synthetic APN inhibitors. Current status on their potential use as therapeutic agents is discussed with regard to toxicity and specificity.
 ...
PMID:Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects. 1621 10

Aminopeptidase N (APN)/CD13 is a type II metalloprotease that belongs to the M1 family of the MA clan, which consists of 967 amino acids with a short N-terminal cytoplasmic domain, a single transmembrane part, and a large cellular ectodomain containing the active site. APN has a molecular weight of 110,000. The APN exists in two forms, namely the membrane aminopeptidase N and the soluble aminopeptidase N. Moreover, it exhibits the presence of various isozymes with different functions. APN is a ubiquitous enzyme present in a wide variety of human organs, tissues and cell types (endothelial, epithelial, fibroblast, leukocyte). It is a multifunctional enzyme, related with tumorigenesis, immune system, pain etc. Furthermore, it also serves as a receptor for coronaviruses and other human viruses. Besides the manifestation of various other functions, APN is also involved in the trimming of antigen and the process of antigen presentation. These functions facilitate the modulation of bioactive peptide responses (pain management, vasopressin release) and influence immune functions and major biological events (cell proliferation, secretion, invasion, angiogenesis) thereby providing treatment options for many kinds of diseases. This review will introduce the structure and main functions of APN briefly.
 ...
PMID:The structure and main functions of aminopeptidase N. 1734 52