Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Omeprazole (OME) is a novel acid secretion inhibitor, believed to act directly on the gastric proton pump, the (H+ + K+)-ATPase. Inhibition of ATPase activity is associated with an incorporation of [14C]OME into gastric vesicles containing the (H+ + K+)-ATPase, and both processes are greatly enhanced if the OME is exposed to acidic pH. This, and other evidence, suggests that the acidic environment of the (H+ + K+)-ATPase generates from OME a reactive intermediate which covalently inhibits the pump. We have compared the means by which the OME was acid-activated with the specificity of inhibition (amount of incorporation of omeprazole required to produce 100% inhibition of K+-stimulated ATPase activity). The stoichiometry of incorporation has been related to the number of detectable catalytic phosphorylation sites in each preparation (an index of the number of functional pumps). In lyophilised gastric vesicles, where the membrane barriers separating the cytoplasmic and luminal faces of the enzyme are substantially destroyed, incubation with OME at pH 6.1 produced a progressive inhibition and incorporation over 120 min. Complete inhibition of K+-ATPase required 13 +/- 3 (SEM; N = 4) moles of OME incorporation per phosphorylation site. In intact gastric vesicles, under conditions shown independently to result in proton pumping and the acidification of the vesicle interior (150 mM KCl, 9 microM valinomycin, 2 mM Mg-ATP pH 7.0), inhibition and incorporation occurred more rapidly (15 min). Complete inhibition of K+-ATPase required only 1.8 +/- 0.15 (SEM; N = 3) moles of OME per phosphorylation site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The specificity of omeprazole as an (H+ + K+)-ATPase inhibitor depends upon the means of its activation. 302 28

Erythrocyte membrane Na+,K+-ATPase activity was measured using a bioluminescence technique in 28 hypertensive patients (24 with essential hypertension, 2 with renovascular hypertension and 2 with hypertension secondary to primary hyperaldosteronism) and in 28 normotensive control subjects matched for age and sex. Erythrocyte Na+,K+-ATPase activity was significantly reduced in the patients with essential hypertension (130.9 +/- 11.4 vs. 186.6 +/- 19.5 nmol ATP/mg prot per h; mean values +/- SEM; p less than 0.05) and in the patients with secondary hypertension. A significant negative correlation was found between erythrocyte Na+,K+-ATPase and systolic blood pressure (r = -0.603; p less than 0.01), but not between Na+,K+-ATPase and plasma renin activity or plasma aldosterone levels. These data confirm the findings of a number of previous studies reporting reduced activity of erythrocyte Na+,K+-ATPase possibly related to the presence of a circulatory inhibitor of sodium pump. The method, based on ATP assay by bioluminescence, presents a high degree of specificity as well as simple, rapid execution.
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PMID:Measurement by bioluminescence technique of erythrocyte membrane Na+,K+-ATPase activity in hypertensive patients. 303 52

The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 +/- 46 (SEM) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 +/- 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 +/- 0.73, significantly higher than in 'non-functional' tumours (1.57 +/- 0.29) or normal tissue (1.77 +/- 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.
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PMID:Increased creatine kinase activity in pituitary tumours of rat and man. 303 50

The coronary efflux of radioactive 3',5'-cyclic adenosine monophosphate (cAMP) and adenosine from isolated guinea pig hearts was measured following selective prelabelling of coronary endothelial adenine nucleotides with 10 nM [2,8,5'-3H] adenosine. Intracoronary infusion of adenosine and its derivatives 5'-N-ethyl-carboxamide-adenosine (NECA), (-)-N6-(R-phenyl-isopropyl)-adenosine (R-PIA), and (+)-N6-(S-phenyl-isopropyl)-adenosine (S-PIA) caused dose-dependent parallel increases in both coronary flow and the coronary efflux of radioactive cAMP with a rank order of potency: NECA greater than R-PIA greater than adenosine greater than S-PIA. In contrast, adenosine receptor stimulation of isolated cardiomyocytes in primary culture decreased the cellular release of cAMP below control levels with a rank order of potency: R-PIA greater than NECA. Under control conditions, coronary efflux of adenosine and cAMP was 34.3 +/- 2.3 and 3.9 +/- 0.8 pmol/min (mean +/- SEM, n = 6), respectively. NECA (12 microM) caused an increase in cardiac cAMP release of 3.8 times and elevated the specific radioactivity of cAMP 5 times to 63.7 +/- 6.0 Ci/mol, a value 11 times greater than the specific radioactivity of tissue ATP. Based on these findings, it was concluded that the coronary endothelium possesses adenosine A2 receptors linked to adenylate cyclase, which are activated in parallel with increases in coronary flow and that cardiomyocyte adenosine receptors are predominantly of the A1 subtype. In addition, the contribution of the coronary endothelium to total cardiac adenosine release was calculated to be 14% using the specific radioactivities of adenosine and cAMP released into the effluent perfusate.
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PMID:Release of adenosine and cyclic AMP from coronary endothelium in isolated guinea pig hearts: relation to coronary flow. 303 94

We studied the cellular mechanism involved in the desensitization of cultured endothelial cells to bradykinin. Bradykinin (10 nmol/l) evoked a rise in the intracellular free calcium concentration [( Cai2+]), measured with the fluorescent probe indo-1, from 137 +/- 30 (+/- SEM) to 623 +/- 101 nmol/l. Cells were desensitized to bradykinin by repetitive stimulation with the peptide over 10 min, after which they no longer responded to bradykinin. However, purinergic stimulation with ATP (10 mumol/l) elicited the same increase in [Cai2+] in endothelial cells desensitized to bradykinin as in cells never exposed to bradykinin. The initial peak of [Cai2+] after stimulation with bradykinin or ATP was not affected by removal of extracellular calcium ions, indicating mobilization of Ca2+ from intracellular stores. Since GTP-binding proteins (G-proteins) are probably involved in the receptor-mediated stimulation of endothelial cells, we also tested the effects of sodium fluoride (NaF), a reported direct stimulator of G-proteins, on endothelial [Cai2+]. NaF (5 mmol/l) increased [Cai2+] to 412 +/- 88 nmol/l in control cells and was equally effective in cells desensitized to bradykinin. We conclude that the homologous desensitization to bradykinin does not occur at the level of intracellular signal transduction but at the level of membrane receptors.
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PMID:Desensitization of the bradykinin-induced rise in intracellular free calcium in cultured endothelial cells. 321 15

The effect of graded ischaemic injury on post-ischaemic myocardium was examined in rat hearts after three 4 min periods of asphyxia. Systolic function under steady state conditions and during isovolumic beats, the content of high energy phosphates and glycogen, and myocardial material properties were determined. Severity of the oxygen deficiency was varied by manipulating myocardial oxygen demand (MVO2) either by rapid atrial pacing or by vagal stimulation. After 20 min of post-asphyxial recovery, steady state haemodynamics were almost normal. In the high MVO2 group (atrial pacing) the dp/dtmax was reduced to 90%(NS). The isovolumic indices of function were decreased in all post-asphyxial groups. This was most pronounced in the high MVO2 group, with a reduction in peak left ventricular systolic pressure to 85.7 (SEM 3.4)% and a decrease in peak left ventricular systolic stress to 82.3(3.9)% (p less than 0.01). The post-asphyxial myocardial performance recovered better in the low MVO2 group (vagal stimulation). Material properties were altered only in the high MVO2 group. The decreased content of ATP and glycogen were comparable in all post-asphyxial groups. A phosphocreatine overshoot phenomenon was most marked in the high MVO2 group: 11.4(2.8) mumol.g-1 v 4.7(0.9) mumol.g-1 (control), p less than 0.01. The results indicate that post-ischaemic contractile dysfunction of reversibly injured is not closely related to the previous O2 deficit or to the functional impairment. We also obtained no correlation between ATP content and material properties in modestly injured post-ischaemic myocardium.
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PMID:Effects of graded intensity of oxygen deficiency on function and energy metabolism in post-ischaemic myocardium. 325 28

MgATP binding to the actomyosin complex is followed by the dissociation of actin and myosin. The rate of this dissociation process was determined from the relationship between the maximum velocity of shortening and the MgATP concentration. It is shown here that the overall dissociation rate is rather similar in different types of muscle fibers. The relation between MgATP concentration and the maximum shortening velocity was investigated in fast and slow fibers and bundles of myofibrils of the iliofibularis muscle of Xenopus laevis at 4 degrees C from which the sarcolemma was either removed mechanically or made permeable by means of a detergent. A small segment of each fiber was used for a histochemical determination of fiber type. At 5 mM MgATP, the fast fibers had a maximum shortening velocity (Vmax) of 1.74 +/- 0.12 Lo/s (mean +/- SEM) (Lo: segment length at a sarcomere length of 2.2 microns). For the slow fibers Vmax was 0.41 +/- 0.15 Lo/s. In both cases, the relationship between Vmax and the ATP concentration followed the hyperbolic Michaelis-Menten relation. A Km of 0.56 +/- 0.06 mM (mean +/- SD) was found for the fast fibers and of 0.16 +/- 0.03 mM for the slow fibers. Assuming that Vmax is mainly determined by the crossbridge detachment rate, the apparent second order dissociation rate for the actomyosin complex in vivo would be 3.8.10(5) M-1s-1 for the fast fibers and 2.9.10(5) M-1 s-1 for the slow fibers. Maximum power output as a function of the MgATP concentration was derived from the force-velocity relationships. At 5 mM MgATP, the maximum power output in fast fibers was (73 +/- 8) mW.g-1 dry weight and (15 +/- 5) mW.g-1 in slow fibers. The Km for MgATP for the maximum power output for the fast fibers was (0.15 +/- 0.03) mM, which is about a factor of 4 lower than the Km for Vmax. The implications of these results are discussed in terms of a kinetic scheme for crossbridge action.
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PMID:Dependency of the force-velocity relationships on Mg ATP in different types of muscle fibers from Xenopus laevis. 326 Aug 2

An isocratic HPLC system has been developed which allows for the rapid (single run of 20 min) measurement of creatine phosphate (PCr) and adenine nucleotides (ATP, ADP and AMP) in extracts from freeze-clamped and freeze-dried myocardial tissues. The separation was achieved at room temperature by using a RP18 column and a dual variable wavelength spectrophotometer, set at 210 and 254 nm. The solvent was 30 mM potassium dihydrogen phosphate, 15 mM tetrabutylammonium hydrogen sulfate, pH 6.7, 19% (v/v) acetonitrile. A distinct separation (confirmed with the retention time of standard sample) of these high energy compounds was achieved. Standard curves were linear. In isolated rat hearts the following values were obtained (mumol/g dry wt, mean +/- SEM): ATP 21.5 +/- 1.3, ADP 4.6 +/- 0.2, AMP 1.5 +/- 1.1 and PCr 32.5 +/- 1.3; which are consistent with previously published values for high energy compounds in this tissue.
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PMID:Simultaneous determination of myocardial creatine phosphate and adenine nucleotides by reversed-phase HPLC. 350 28

A possible mechanism to regulate body weight during a high calorie intake may be an increased metabolic rate in skeletal muscle. To approach this hypothesis the energy metabolites, ATP, phosphocreatine, creatine, glycogen and lactate were measured in biopsies from the quadriceps femoris muscle. Concomitantly the function of the adductor pollicis muscle was studied as assessed after electrical stimulation of the ulnar nerve. The muscle function variables were, force of contraction at 5, 10, 20, and 50 Hz of stimulation, relaxation rate, and endurance. Eight obese women were studied before gastroplastic surgery and 6 months postoperatively and a weight loss of 19.4 +/- 3.4% (mean +/- SEM). Preoperatively ATP, phosphocreatine, glycogen, and lactate were significantly decreased and the same pattern was found postoperatively. These findings can be related to a low production of energy-rich phosphates or a high energy utilization. Both pre- and postoperatively there was, a decreased force of contraction at 10 Hz of stimulation (p less than 0.001), a faster relaxation rate (p less than 0.01) and a normal endurance. These functional results indicate a high metabolic rate. At admission a decreased serum insulin level indicated a moderate insulin resistance which was normalized after the weight loss. The triiodothyronine concentration was normal before and after operation. In conclusion our findings of changed muscle energy metabolite concentrations and altered muscle function indicate a high metabolic rate in skeletal muscle in obese women. This may be an adaptation in skeletal muscle energy metabolism to a high body weight.
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PMID:Skeletal muscle function and metabolism in obese women. 354 Mar 33

During exercise, ATP is converted to ADP and AMP to supply energy for muscular contraction. It is then regenerated via various pathways of intermediary metabolism. However, with high levels of exercise, net ATP degradation in muscle occurs. In exercise and other clinical situations, adenine nucleotide degradation leads to an accumulation of degradative purine products including hypoxanthine. In an effort to monitor events of energy metabolism, we examined plasma hypoxanthine levels at various exercise intensities. Peak plasma hypoxanthine levels after maximal exercise (18.9 +/- 2.6 microM, mean +/- SEM) were significantly greater than resting levels (1.1 +/- 0.1 microM; p less than 0.001). Hypoxanthine levels after steady state exercise at 52, 76, and 97% of ventilatory threshold did not exceed resting levels. However, plasma hypoxanthine rose significantly after exercise at 124% of ventilatory threshold (6.3 +/- 1.0 microM; p less than 0.01) and at 152% of ventilatory threshold (17.0 +/- 3.6 microM; p less than 0.001). Exercise at subventilatory threshold intensity (74% of ventilatory threshold) for a prolonged time period, such that total work equaled that performed at 152% of ventilatory threshold, did not elevate hypoxanthine levels (0.46 +/- 0.1 microM) above resting values. We conclude that elevation of plasma hypoxanthine levels occur during exercise at intensities that exceed the ventilatory threshold and indicate that net adenine nucleotide degradation has occurred.
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PMID:Plasma hypoxanthine and exercise. 360 51


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