Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ca binding in the red blood cell (RBC) membrane of spontaneously hypertensive rats (SHR) and of patients with essential hypertension was studied. Under conditions of physiological concentration of free Ca in the incubation medium of RBC the outer part of the membrane binds 393 +/- 32 and 435 +/- 30 nmole of Ca per ml of RBC in rats and humans, respectively, without essential differences in the amount of Ca in hypertensive individuals as compared to the normotensive controls. The membrane of red blood cell ghosts (RBCgh) at concentrations of free Ca corresponding to its intracellular concentration binds 4.28 +/- 0.39 and 3.53 +/- 0.15 nmole of Ca per mg of protein of RBCgh in rats and humans, respectively. This part of membrane-bound Ca pool (most probably related to the inner part of the red blood cell membrane) is reduced by 48% in SHR and by 28% in patients with essential hypertension as compared to normotensive controls. It is suggested that the decrease of Ca binding ability of the RBC membrane in both types of hypertension studied may be a pattern of a more widespread cell membrane defect.
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PMID:Decrease of calcium binding by the red blood cell membrane in spontaneously hypertensive rats and in essential hypertension. 57 Nov 15

The primary mechanism of regulation of smooth muscle contraction involves the phosphorylation of myosin catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase. However, additional mechanisms, both Ca(2+)-dependent and Ca(2+)-independent, can modulate the contractile state of smooth muscle. Protein kinase C was first implicated in the regulation of smooth muscle contraction with the observation that phorbol esters induce slowly developing, sustained contractions. Protein kinase C occurs in at least four Ca(2+)-dependent (alpha, beta I, beta II, and gamma) and four Ca(2+)-independent (delta, epsilon, zeta, and eta) isoenzymes. Only the alpha, beta, epsilon, and zeta isoenzymes have been identified in smooth muscle. Both classes of isoenzymes have been implicated in the regulation of smooth muscle contraction. However, the physiologically important protein substrates of protein kinase C have not yet been identified. Specific isoenzymes may be activated by different contractile agonists, and individual isoenzymes exhibit some degree of substrate specificity. Prolonged activation of protein kinase C can result in its proteolysis to the constitutively active catalytic fragment protein kinase M, which would dissociate from the sarcolemma and phosphorylate proteins such as myosin that are inaccessible to membrane-bound protein kinase C. Protein kinase M induces relaxation of demembranated smooth muscle fibers contracted at submaximal Ca2+ concentrations. We suggest that protein kinase C plays two distinct roles in regulating smooth muscle contractility. Stimuli triggering phosphoinositide turnover or phosphatidylcholine hydrolysis induce translocation of protein kinase C (probably specific isoenzymes) to the sarcolemma, phosphorylation of protein, and a slow contraction. Prolonged association of the kinase with the membrane may lead to proteolysis and release into the cytosol of protein kinase M, resulting in myosin phosphorylation and relaxation.
Hypertension 1992 Nov
PMID:Protein kinase C of smooth muscle. 142 8

1. The two isozymes of human angiotensin converting enzyme (ACE; EC 3.4.15.1) have recently been cloned and sequenced. 2. The larger, endothelial isozyme has two highly similar internal domains each bearing a putative catalytic site. In contrast the smaller, testicular isozyme has a single catalytic site corresponding to the C-terminal domain of endothelial ACE and represents the ancestral, non-duplicated form of the gene. 3. Both isozymes are anchored in the plasma membrane by a single hydrophobic transmembrane polypeptide located near the C-terminus, and both are extensively N-glycosylated. 4. The testicular isozyme may also be O-glycosylated. 5. The soluble form of ACE in plasma, seminal fluid and other body fluids appears to be derived from the membrane-bound endothelial isozyme by a post-translational modification. 6. ACE has a complex substrate specificity with peptidyl tripeptidase or endopeptidase action on certain peptides, as well as the classical peptidyl dipeptidase activity. 7. Numerous potent inhibitors of the enzyme have been developed and used successfully in the treatment of hypertension, but some of the observed side effects may be due to inhibition of other zinc metalloenzymes. 8. Both endothelial and testicular ACE are highly conserved between species, indicative of the essential role(s) of the enzyme in blood pressure regulation and other physiological processes.
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PMID:Angiotensin converting enzyme: implications from molecular biology for its physiological functions. 165 Jul 17

When big endothelin-1 (big ET-1, 1-39) was incubated with the membrane fraction obtained from cultured endothelial cells (ECs) at pH 7.0 for 6 h, the immunoreactive (ir) ET in the reaction mixture was markedly increased. Phosphoramidon, a metalloproteinase inhibitor, as well as metal chelators specifically suppressed the above increase. Using reverse-phase high-performance liquid chromatography, ir-ET was confirmed to be ET-1[1-21]. In addition, we noted that the alterations in ET-1 correlated with those in the C-terminal fragment (CTF, 22-39) of big ET-1. When cultured ECs were incubated with phosphoramidon, time-dependent secretion of ET-1 and CTF from the cells was markedly suppressed. In contrast, the secretion of big ET-1 was increased by phosphoramidon. Thiorphan, a specific inhibitor of neutral endopeptidase 24.11, was without effect on the secretion of ET-related peptides. Moreover, phosphoramidon potently inhibited the hypertensive effect of big ET-1 without affecting the ET-1-induced hypertension in anesthetized rats. From these findings, it seems reasonable to consider that phosphoramidon-sensitive and membrane-bound metalloproteinase, which is not a neutral endopeptidase 24.11, is the most plausible candidate for big ET-1-converting enzyme in vivo.
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PMID:Conversion of big endothelin-1 to endothelin-1 by phosphoramidon-sensitive metalloproteinase derived from aortic endothelial cells. 172 35

Alterations in activity of membrane-bound Ca2(+)-ATPases were shown to depend on the rate of lipid peroxidation in cell membranes of patients with hypertension during the period of crisis. On the basis from these results antioxidants and Ca2(+)-antagonistic drugs could be used for treatment of hypertensive crisis. Monitoring of the disease is possible by means of estimation of the membrane-bound Ca2(+)-ATPases activity.
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PMID:[The function of membrane Ca-ATPases and nonenzymatic peroxidation of membrane lipids in patients with hypertension]. 214 37

We report an unusual case of malignant mixed mesodermal tumor of the uterine corpus associated with various symptoms related to overproduction of catecholamine by the tumor cells. Histologically, the tumor was dominated by carcinomatous epithelium with foci of malignant mesenchyma. The type of epithelium was endometrioid with papillary adenocarcinomas containing foci of malignant squamous epithelium. The malignant mesenchyma consisted mainly of a fibrous stroma with many large and bizarre cells and spindle cells mimicking leiomyosarcoma, many of which were pleomorphic and contained large bizarre hyperchromatic nuclei. Foci of atypical adult-type cartilage and neoplastic osteoid formation were noted. In the tumor tissue, membrane-bound neurosecretory-type cytoplasmic granules were demonstrated by electron microscopy and polypeptide hormone synthesis was demonstrated by immunohistochemistry. Furthermore, the patient suffered frequent attacks of sudden hypertension with hypercatecholaminemia.
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PMID:A malignant mixed mesodermal tumor of the uterine corpus with hypercatecholaminemia. 216 44

Changes in our concepts of angiotensin I converting enzyme are reviewed briefly. The actions of this enzyme go beyond liberating angiotensin II from angiotensin I or inactivating bradykinin. Its very wide distribution in the body and its activity in vitro indicate involvement in the metabolism of other biologically active peptides. The recent molecular cloning of the human enzyme confirmed the existence of a hydrophobic C-terminal peptide that forms the short transmembrane domain of this plasma membrane-bound enzyme. The much longer external portion contains two homologous active site domains but probably only one functional active center. Finally, in spite of the great progress made in studying angiotensin converting enzyme, there are many challenging problems waiting to be solved.
Hypertension 1990 Oct
PMID:Angiotensin I converting enzyme and the changes in our concepts through the years. Lewis K. Dahl memorial lecture. 217 Feb 73

In order to determine whether phosphoinositide metabolism is altered in hypertensive cardiac hypertrophy, phospholipase C (PLC) and protein kinase C activities were measured in hearts from 4- and 20-week-old spontaneously hypertensive rats (SHR) and age-matched, normotensive Wistar-Kyoto rats (WKY). PLC activities were assayed using phosphatidylinositol (PI) and phosphatidylinositol-4,5-bisphosphate (PIP2) as substrates to assess the substrate specificity. PI-hydrolyzing PLC activity (PI-PLC) was predominantly located in the cytosol, and its activity was similar in both strains. Membrane-bound PIP2-hydrolyzing PLC activity (PIP2-PLC) was significantly lower in 20-week-old SHR than in WKY, but there was no significant difference in soluble PIP2-PLC. Protein kinase C activity was significantly elevated in 20-week-old SHR and Ca2(+)-phospholipid-dependent phosphorylation was observed in the proteins of molecular weight 26, 32, 43, and 95 KDa. In 4-week-old prehypertensive SHR, there were no significant differences in PI-PLC, PIP2-PLC, or protein kinase C activities as compared with age-matched WKY. These data demonstrated that protein kinase C and membrane-bound PIP2-PLC are altered during the period of hypertension development. These alterations may have important roles in the development or maintenance of hypertensive cardiac hypertrophy in SHR.
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PMID:Alterations of phosphoinositide-specific phospholipase C and protein kinase C in the myocardium of spontaneously hypertensive rats. 217 34

The mechanism of action of calcium channel modulators, a class of drugs that includes 3 chemical groups--1,4-dihydropyridines, phenylalkylamines and benzothiazepines--has been extensively reviewed. The best known representatives of these 3 groups are nifedipine, verapamil and diltiazem, respectively. These drugs bind reversibly, stereospecifically and with high affinity to both the membrane-bound and the purified receptor complex. Non-dihydropyridines allosterically regulate dihydropyridine binding. This has been shown by using (-) [3H]202-791 and (+) [3H]PN200-110 as labeled ligands. The purified receptor complex that possesses binding sites for all 3 chemical groups is likely to be related to the voltage-dependent calcium channel. As the result of a drug-receptor interaction, voltage-dependent calcium channels are either activated or inactivated. The drugs that activate channels act by promoting long-lasting channel openings. The drugs that inhibit calcium channels, the calcium entry-blocking agents, act by preventing channel openings upon membrane depolarization. A complex pharmacologic, electrophysiologic, biochemical, immunologic and molecular genetic approach is required to determine the molecular mechanism of action of calcium channel modulators. Clinically, calcium entry-blocking agents are recommended for the treatment of angina pectoris, hypertension, posthemorrhagic cerebral vasospasm, supraventricular tachycardia, migraine and asthma and the protection of the ischemic myocardium.
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PMID:Receptor pharmacology of calcium entry blocking agents. 243 27

A case of beta galactosidase deficiency is described in a 20-month-old boy. The child was hospitalized at 4 months of age for malabsorption syndrome. Biopsies of the small intestine and liver were performed and electron microscopy of the liver specimens strongly suggested a gangliosidosis. The cytoplasm of macrophages, Kupffer cells and hepatocytes contained membrane-bound lysosomes with a granular, fibrillar appearance and tubular structures interpreted as ganglioside deposits. Enzymatic deficiency was confirmed by biochemical investigation of leukocytes from both the patient and members of his immediate family. Although visceromegaly is typical of Landing disease, symptoms of malabsorption and hypertension have not been reported in its course.
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PMID:Landing disease, GM1 generalized gangliosidosis, and malabsorption syndrome. 250 73


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