Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The enzymatic properties of plasma membrane-bound Na+, K+-ATPase [EC 3.6.1.3], isolated with high specific activity and in good yield from pig thyroid cells, were examined. The enzyme activity required the presence of both Na+ and K+ at physiological concentrations; it exhibited high sensitivity to K+ and an absolute requirement for Na+. It showed highly specific requirement for Mg2+ and ATP. The apparent Km for ATP was 0.14 mM under the assay conditions. Arrhenius plots had a point of inflection at about 22 degrees C, activation energies being 24.2 kcal/mol at 5-22 degrees C and 19.0 kcal/mol at 22-40 degrees C. In addition to ouabain, the ATPase was strongly inhibited by fluoride and the SH-blocking reagent, PCMB. Iodide and TSH had no appreciable effect on the enzyme activity.
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PMID:Properties of the Na+, K+-stimulated adenosine triphosphatase system associated with the plasma membrane of pig thyroid glands. 14 Aug 65

The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined. The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma. The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma. The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5'-nucleotidase activity did not change. These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.
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PMID:Changes in cyclic nucleotides of rat thyroid by chronic administration of LATS and TSH. 21 Jun 9

Changes in the content of cyclic nucleotides (cAMP and cGMP) and related enzyme activities were observed in the rat thyroid, pituitary and plasma during the prolonged increase of endogenous TSH produced by treatment with methylthiouracil (MTU). Experiments were performed after 4 weeks treatment with MTU. The wet weight and cAMP content per wet weight of the thyroid increased 3 and 1.4 times respectively, but cGMP showed a slight decrease. Pituitary weight increased 1.3 times, but cAMP and cGMP content did not change. The cAMP level in plasma also increased about 1.3 times, but cGMP did not increase. The cAMP-phosphodiesterase activity in the thyroid, pituitary and plasma was increased 1.9, 1.4 and 1.3 times respectively after MTU treatment, while cGMP-phosphodiesterase showed no significant change. ATPase activity in the thyroid and pituitary was also increased more than 1.5 times after MTU treatment, while 5'-nucleotidase activitity decreased remarkably. These data indicate that the metabolism of the cyclic nucleotide system in the thyroid is stimulated by TSH.
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PMID:Changes in the cyclic nucleotides of rat thyroid, pituitary and plasma caused by methylthiouracil treatment. 21 61

Transgenic mice for the promoter sequence of bovine arginine vasopressin (AVP) gene fused to large SV40 T-antigen coding sequence develop pituitary tumors and insulin-producing pancreatic tumors. In order to establish the cellular composition of the pituitary tumors, histological, immunocytochemical, in situ hybridization, and electron microscopic technics were applied. Pituitary anterior lobe tumors were identified in 10 out of 14 glands examined. In 2 of these cases, intermediate lobe tumors were also found. The anterior lobe tumors contained a variable number of GH immunoreactive cells. In situ hybridization performed in 7 cases revealed a diffuse distribution of GH messenger RNA over all tumor cells. Ultrastructurally, the tumors contained undifferentiated cells with very small secretory granules and rare cells showing some resemblance to somatotrophs. The results indicate that these pituitary tumors are composed of undifferentiated somatotrophs. The presence of a few PRL immunoreactive cells in four tumors and scattered TSH immunoreactive cells in two tumors supports the view that somatotrophs have the potential to produce PRL and TSH. The intermediate lobe tumors were immunoreactive for ACTH and intensely positive for POMC mRNA. In the nontumorous adenohypophyses, no hyperplasia of any cell type was noted. Several GH immunoreactive cells exhibited pleomorphic, giant nuclei and mitoses. In conclusion, the majority of transgenic mice for AVP/large T-antigen develop pituitary tumors originating in and composed of somatotrophs. Less frequently, intermediary lobe tumors were present as well. AVP/SV40 transgenic mice provide a unique experimental model for somatotroph tumors that are neither preceded by, nor associated with somatotroph hyperplasia.
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PMID:Morphology of adenohypophysial tumors in mice transgenic for vasopressin-SV40 hybrid oncogene. 131 26

Iodolipids are the possible mediators of excess iodide in thyroid autoregulation. Previous work from our laboratory has shown that 14-iodo-15-hydroxy-5,8,11 eicosatrienoic acid (I-HO-A) and its omega lactone (IL-w) mimic the inhibitory action of excess iodide upon several parameters of thyroid metabolism. The present experiments were performed in order to study the mechanism of the inhibitory effect of I-HO-A and IL-w on 2-deoxy-D-glucose (DOG) and aminoisobutyric acid (AIB) uptake by calf slices. I-HO-A, IL-w and KI 0.1 mM caused a 33, 31 and 25% inhibition, respectively, of AIB uptake. The presence of 0.1 mM methimazole (MMI) only reversed the effect of KI. The transport of DOG was inhibited by both compounds: I-HO-A caused a 62% decrease, while IL-w produced a 64% inhibition; and MMI failed to relieve their action. On the contrary, the 33% inhibition caused by KI disappeared when MMI was present. Taking into account that AIB and DOG transport across the membrane requires energy, supplied by Na-K-ATPase, changes in its activity were studied. TSH (10 mU/ml) produced a 74% increase in the enzyme activity which was significantly blocked by KI (82%), I-HO-A (100%) and IL-w (100%). Basal enzyme activity was impaired by IL-w (33%), but not by KI. These results were correlated with the decrease of DOG uptake produced by 1 mM ouabain. Tissue specificity effect of iodoarachidonates was demonstrated by the absence of action on DOG transport in kidney and liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroid autoregulation: evidence for an action of iodoarachidonates and iodide at the cell membrane level. 166 78

We investigated the effect of hydrogen peroxide on the process of thyroid hormone formation in a physiologic culture system of porcine thyroid follicles that we recently established. Porcine thyroid follicles cultured in medium containing 1 mU/mL TSH were exposed to 0 to 500 microM hydrogen peroxide in the presence of 0.1 microCi carrier-free Na125 and sodium iodide for 2 h. Iodide uptake and iodine organification were measured in this incubation system. The kinetics of iodide uptake were used to explain the action of hydrogen peroxide. In addition, cAMP content and Na+,K(+)-ATPase activity (an enzyme necessary for iodide uptake) were measured to investigate the mechanism of hydrogen peroxide action. Hydrogen peroxide at concentrations of 100, 200, and 500 microM inhibited iodide uptake in a dose-dependent manner. Iodide organification was inhibited only when the concentration of hydrogen peroxide was greater than 200 microM. The kinetics of iodide uptake indicated that hydrogen peroxide was a noncompetitive inhibitor with iodide. Inhibition of iodide uptake and iodine organification by hydrogen peroxide were not mediated by alteration of cAMP content of Na+,K(+)-ATPase activity, since exposure to even 500 microM hydrogen peroxide did not change these parameters in the follicle when compared with those of control samples. Our results suggest that the iodide transport system in the thyroid follicle is inhibited at 200 microM hydrogen peroxide or greater.
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PMID:Hydrogen peroxide inhibits iodide uptake and iodine organification in cultured porcine thyroid follicles. 166 18

Iodide uptake by primary cultures of turtle thyroid follicular cells is directly proportional to the Na+ concentration and is inversely proportional to the HCO3- concentration in culture medium, but is not affected by the Cl- concentration. Addition of 4,4'-di-isothiocyano-2,2'-stilbene disulphonate (DIDS; 10 mumol/l and higher doses) to medium containing different concentrations of Na+ (5-140 mmol/l), HCO3- (0-40 mmol/l) and Cl- (120 mmol/l) generally enhanced iodide uptake by the cultured cells; however, there was no significant effect in Na+-free and in low Cl- (90 mmol/l and less) medium. The inhibitory effects on iodide uptake of ouabain, frusemide and perchlorate were attenuated by DIDS which also antagonized the stimulatory effects on iodide uptake of TSH, although both DIDS and TSH increased the 125I- cell/medium ratio when they were given alone. At doses of 100 mumol/l and higher, DIDS lowered the intracellular pH of cultured cells when the pH of the medium was maintained at a constant level. It also increased the intracellular Cl- concentration, but had no effect on intracellular Na+ or K+. The input and specific resistances of cell membranes in cultured thyroid cells and in isolated thyroid slices increased (decreased conductance) after adding DIDS to the perfusion fluids. Both Na+/K+- and HCO3(-)-ATPase activities in homogenates of turtle thyroid tissue were inhibited by DIDS. Results from this investigation demonstrate (1) that in addition to preventing the leak of iodide from thyroid cells, DIDS may act to increase the sensitivity of the Na+-anion carrier to I- and thereby increases iodide uptake, and (2) that a HCO3(-)-Cl- exchange system is present in the thyroid cell membrane and appears to be linked to the transport of iodide into thyroid cells.
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PMID:Effects of 4,4'-di-isothiocyano-2,2'-stilbene disulphonate on iodide uptake by primary cultures of turtle thyroid follicular cells. 244 78

On the basis of rat model of congenital hypothyroidism, the following problems were investigated: (1) The biochemical changes of DNA amount in cerebrum, and increase of DNA concentration & decline of protein/DNA in cerebellum. (2) The mitochondria ATPase activity of the cells in cerebral cortex was significantly diminished in hypothyroidism, suggesting that energy metabolism of brain was affected by thyroid hormone. (3) The serum T4 level of hypothyroid offsprings was markedly decreased with increase of serum TSH concentration, while the serum T3 content showed no change. However, 131I uptake rate of thyroid was elevated with peak ahead of time in hypothyroid rats. (4) All the hypothyroid rats were accompanied with delayed body weight growth and decreased weight of brain and several other organs. (5) After replacement therapy with thyroid all the indices mentioned above were improved.
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PMID:[Influence of congenital hypothyroidism on the developing rat brain and improvement after thyroid replacement therapy]. 253 92

When cultured on collagen coated nitrocellulose filters, thyroid epithelial cells form morphologically and functionally polarized monolayers. The bioelectric parameters of these monolayers were measured after mounting in Ussing chambers; transepithelial potential (Vab), short circuit current (Isc) and transepithelial resistance were respectively 12 +/- 1 mV (apical side negative), 3.8 +/- 0.2 microA cm-2 and 3250 +/- 214 omega cm2 (mean +/- SEM, n = 75). Eighty two percent of the short circuit current was related to sodium absorption as shown by inhibition by apical amiloride (Km = 0.2 microM) and by basal ouabain (K1/2 = 0.3 microM). Amphotericin B (5-25 micrograms/ml) added to the apical bath increased Isc suggesting an apical rate-limiting step. Step by step replacement of choline by Na+ in a Na+-free medium resulted in a progressive increase in Vab and Isc with half maximal effect at 20 +/- 1 mM Na+. Thyrotropin (TSH) increased Isc and Vab in a biphasic way with a transient maximum after 5 min and a plateau after 20 min (about four times the basal level at 100 microU/ml TSH). This increase in sodium transport was also inhibited by apical amiloride. Thus, in culture, the thyroid cell monolayer behaves as a tight sodium absorbing epithelium controlled by TSH, with a rate limiting apical sodium channel as the entry mechanism and a basolateral Na+, K+-ATPase as the electromotive force.
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PMID:The thyroid cell monolayer in culture. A tight sodium absorbing epithelium. 255 Aug 88

The effects of omeprazole (an H+, K+ -ATPase inhibitor) on thyroid parameters in rats have been examined. SK&F Wistar rats were dosed orally with omeprazole (up to 500 mg kg-1) or vehicle. Treatment for 7 or 14 days resulted in generally decreased plasma T3 concentrations in males (with little change or slight increases in females) and increased serum TSH concentrations (22%-68% increases). No changes were detected in thyroid 125I uptake or organification. Liver 5'-deiodinase activity was decreased in male rats after 7 days treatment. Thyroxine clearance was not altered after a single dose of omeprazole. In-vitro studies showed omeprazole to be only a weak inhibitor of TSH-stimulated 125I organification in cultured porcine thyrocytes. It is concluded that omeprazole has weak effects on the pituitary-thyroid-liver axis, its main action being to inhibit the peripheral deiodination of thyroid hormones.
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PMID:Studies on the effects of omeprazole on thyroid function in the rat. 257 58


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