Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prednisolone-3,20-bisguanylhydrazone (PBGH), a steroid derivative, has been shown to inhibit Na+,K+-ATPase isolated from guinea-pig heart or kidney in concentrations significantly lower than those required to inhibit the enzyme obtained from other sources. Because Na+,K+-ATPases obtained from guinea-pig heart or kidney are predominantly of the alpha isoform, the hypothesis that PBGH selectively inhibits the alpha isoform over alpha (+) isoform of the enzyme was tested. Sodium dodecylsulfate polyacrylamide gel electrophoresis of the enzyme preparations revealed the presence of only the higher mobility, alpha isoform in guinea-pig heart and ferret kidney, whereas those from guinea-pig brain, dog brain and ferret heart showed both high and low mobility isoforms corresponding to alpha and alpha (+) isoforms. Na+,K+-ATPase obtained from the guinea-pig heart was most sensitive to PBGH and those isolated from ferret heart or ferret kidney had the lowest sensitivity. Enzyme preparations obtained from dog brain, dog heart or guinea-pig brain had intermediate sensitivity. This spectrum of enzyme sensitivity to PBGH was markedly different from that to ouabain. In ferret heart Na+,K+-ATPase, a low concentration of PBGH preferentially inhibited [3H]ouabain binding to the high affinity ouabain binding sites (alpha(+) isoform). These results indicate that PBGH is not a specific inhibitor of the alpha isoforms of Na+,K+-ATPase. Affinity of the enzyme for PBGH is determined by the species and tissue rather than isoforms of Na+,K+-ATPase.
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PMID:Cardiac Na+,K+-ATPase isoenzymes: sensitivity to prednisolone bisguanylhydrazone. 285 75

Thirty minutes after experimental spinal cord contusion (500 gm-cm) injury, cats were treated with an initial intravenous dose of either vehicle (V) or 30 mg/kg of Solu-Medrol sterile powder (methylprednisolone sodium succinate; MPSS). Two hours later, cats received a second intravenous injection of either V or 15 mg/kg MPSS, giving three treatment groups: V/V; MPSS/V; MPSS/MPSS. At 4 1/2 hours following injury of the cat lumbar spinal cord, the gray and white matter neurofilament protein content was reduced by over 70% within the injured segment of V/V-treated animals. The three major cat spinal cord neurofilament protein subunits of 200,000, 152,000, and 76,000 daltons were reduced in parallel by the injury. Treatment of cats with a single 30-mg/kg dose of MPSS (MPSS/V) provided a clear, although not significant, protection against neurofilament degradation compared with V/V-treated cats when measured at 4 1/2 hours after injury. The lactic acid content of the injured spinal cord segment at 4 1/2 hours after injury was significantly elevated in both V/V- and MPSS/V-treated cats, while the adenosine triphosphate (ATP) content, total adenylates, and energy charge were significantly reduced. The administration of a second intravenous 15-mg/kg dose of MPSS 2 hours after the initial 30-mg/kg dose (MPSS/MPSS) provided complete (p less than 0.01) preservation of neurofilaments within the injured spinal cord segment measured at 4 1/2 hours after injury. The levels of lactate, ATP, total adenylates, and tissue energy charge in MPSS/MPSS-treated cats were not different from those of uninjured spinal cords following laminectomy. The (Na+ + K+)-ATPase activity in the injured spinal segment was enhanced, although highly variable, in MPSS/V-treated animals. On the other hand, spinal cord enzyme activity was significantly and consistently elevated in the MPSS/MPSS-treated group. The results demonstrate that a 30-mg/kg dose of MPSS followed at 2 hours by a 15-mg/kg dose provides significantly better protection against injury-induced ischemia and Ca++-dependent neurofilament degradation than a single 30-mg/kg dose. These findings are in agreement with the spinal cord tissue pharmacokinetics and time-action characteristics of methylprednisolone observed in earlier studies.
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PMID:Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism. 653 14

A cardinal feature of organ-specific autoimmunity is destructive pathology in the target organ. In human and experimental models of autoimmune gastritis, mononuclear cell infiltration and cellular destruction in the gastric mucosa are disease hallmarks. Strategies to cure autoimmune disease must not only establish immunological tolerance to autoantigen, but also rid the organ of pathogenic autoreactive cells. The present study has assessed the effect of prednisolone treatment in clearing the inflammatory infiltrate in experimental autoimmune gastritis and in preventing disease relapse in athymic compared with euthymic mice. Experimental autoimmune gastritis was induced by neonatal thymectomy or by transgenic expression of GM-CSF (PC-GMCSF mice). Groups of mice were treated with prednisolone (10 mg/kg per day) for 10 weeks or with prednisolone for 10 weeks followed by 10 weeks without prednisolone. Stomachs were examined for gross morphological changes, and by histology and immunohistochemistry for composition of inflammatory infiltrate and gastric mucosal integrity. Autoantibody to gastric H+/K+ ATPase was determined by ELISA. Prednisolone promoted remission of gastritis in both mouse models of experimental autoimmune gastritis, evident by reduction in stomach size, clearing of gastric inflammatory infiltrate, and regeneration of the gastric mucosa. Prednisolone withdrawal resulted in disease relapse in all PC-GMCSF mice, whereas approximately 40% of neonatal thymectomy mice retained normal stomach morphology and remained free of gastric pathology. It is concluded that prednisolone promotes remission and gastric mucosal regeneration in experimental autoimmune gastritis. Prolonged remission of autoimmune gastritis in some athymic mice suggests a role for the thymus in disease relapse.
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PMID:Prednisolone promotes remission and gastric mucosal regeneration in experimental autoimmune gastritis. 1671 Aug 33