Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns.
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PMID:Overview of medical therapy of peptic ulcer disease. 218 24

The concentration dependence of the chemical shifts for the protons H-2, H-8 and H-1' of ATP has been measured in D2O at 27 degrees C under several degrees of protonation in the pD range from 1.5 to 8.4. The results at pD greater than 4.5 are consistent with the isodesmic model of indefinite noncooperative stacking, while those at pD less than 4.5 indicate a preference for the formation of dimeric stacks. The stacking tendency follows the series, ATP4- (K = 1.3 M-1) less than D(ATP)3- (2.1 M-1) less than 1:1 ratio of D(ATP)3-/D2(ATP)-2- (6.0 M-1) much less than D2(ATP)2- (approximately 200 M-1) much greater than D3(ATP)- (K approximately less than 17 M-1) (for reasons of comparison all constants are expressed in the isodesmic model). These results are compared with previous data for adenosine [Ado (K = 15 M-1) greater than 1:1 ratio of Ado/D(Ado)+ (6.0 M-1) greater than D(Ado)+ (0.9 M-1)] and AMP [AMP2- (K = 2.1 M-1) less than D(AMP)- (3.4 M-1) less than 1:1 ratio of D(AMP)-/D2(AMP) +/- (5.6 M-1) greater than D2(AMP) +/- (approximately equal to 2 M-1) greater than D3(AMP)+ (K less than or equal to 1 M-1)] to facilitate the interpretation of the results for the ATP systems. Stack formation of H2(ATP)2- is clearly favored by additional ionic interactions; this is confirmed by measuring via potentiometric pH titrations the acidity constants of H2(ATP)2- in solutions containing different concentrations of ATP. It is suggested that in the [H2(ATP)]4-(2) dimer intermolecular ion pairs (and hydrogen bonds) are formed between the H+(N-1) site of one H2(ATP)2- and the gamma-P(OH)(O)-2 group of the other; in this way (a) the stack is further stabilized, and (b) the positive charges at the adenine residues are compensated (otherwise repulsion would occur as is evident from the adenosine systems). A detailed structure for the [H2(ATP)4-(2) dimer is proposed and some implications of the described stacking properties of ATP for biological systems are indicated.
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PMID:Influence of the protonation degree on the self-association properties of adenosine 5'-triphosphate (ATP). 282 46

The concentration dependence of the chemical shifts of the protons H-2, H-8 and H-1' for 2'-, 3'- and 5'-AMP2- and of the protons H-2, H-7, H-8 and H-1' for tubercidin 5'-monophosphate (= 7-deaza-AMP2-; TuMP2-) has been measured in D2O at 27 degrees C to elucidate the self-association of the nucleoside monophosphates (NMPs). The results are consistent with the isodesmic model of indefinite non-cooperative stacking; the association constants for all four NMPs are very similar: K approximately 2 M-1. These 1H-NMR measurements and those on the dependence of the chemical shifts on the pD of the solutions indicate that the NMP2- species exist predominately in the anti conformation. Comparison of the shift data for 5'-TuMP and 5'-AMP shows that no hydrogen bonding between N-7 and -PO3H- occurs; hence, the previously observed and confirmed 'wrongway' chemical shift [Martin, R. B. (1985) Acc. Chem. Res 18, 32] connected with the deprotonation of the -PO3H- group most probably results from the anisotropic properties of the phosphate group which is in the anti conformation close to N-7. From the dependence between the chemical shift and the pD of the solutions the acidity constants were calculated for the four protonated NMPs, and for adenosine and D-ribose 5'-monophosphate. The measurements also allow an estimation of the first acidity constant of H3(5'-AMP)+ (pKDD3(AMP) = 0.9 and pKHH3(AMP) = 0.4). The values for pKHH2(NMP) and pKHH(NMP) were also determined from potentiometric pH titrations in aqueous solution (I = 0.1 M, NaNO3; 25 degrees C). The agreement of the results obtained by the two methods is excellent. The position of the phosphate group at the ribose moiety and the presence of N-7 in the base moiety influence somewhat the acid-base properties of the mentioned NMPs. Measurements with 5'-AMP in 50% (v/v) aqueous dioxane show that lowering of the solvent polarity facilitates removal of the proton from the H+(N-1) site while the -PO2-3 group becomes more basic; this increases the pH range in which the monoprotonated H(5'-AMP)- species is stable and which is now also extended into the physiological pH region. Some consequences of this observation for biological systems are indicated.
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PMID:Self-association and protonation of adenosine 5'-monophosphate in comparison with its 2'- and 3'-analogues and tubercidin 5'-monophosphate (7-deaza-AMP). 302 2

Following previous demonstration that isoproterenol stimulated and norepinephrine inhibited gastric acid secretion induced by secretagogues, role of adrenergic agonists was studied by measuring acidity the peptic activity of the effluent of the perfused rat stomach. Response of gastric secretion to isoproterenol was increased by theophylline treatment but was not affected by metiamide treatment. N6, O2'-Dibutyryladenosine 3', 5'-cyclic monophosphoric acid sodium salt monohydride (dibutyryl-c-AMP) stimulated gastric secretion in a dose-dependent manner. These results suggest the possibility that the action of isoproterenol in gastric acid secretion is mediated by c-AMP. However, gastric secretion induced by pentagastrin, histamine, or carbamylcholine was not affected by theophylline treatment. N2, O2'-Dibutyrylguanosine 3', 5'-cyclic monophosphoric acid sodium salt (dibutyryl-c-GMP) did not exert any effect on gastric secretion. Depression of pentagastrin-induced gastric secretion by norepinephrine was reversed by EGTA infusion. Moreover, Ca2+, depressed pentagastrin-induced gastric secretion. These results suggest that the action of norepinephrine is closely related to the concentration of Ca2+.
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PMID:Role of adrenergic agonists on gastric secretion in the rat. 611 Jul 14

The acid-catalyzed hydrolysis of adenosine 5'-triphosphate (ATP) has been found to give rise both to adenosine 5'-diphosphate (ADP) and inorganic phosphate and to adenosine 5'-phosphate (AMP) and inorganic pyrophosphate. Kinetic and isotope studies on the mechanism of hydrolysis of ATP therefore depend on a knowledge of the mechanism of hydrolysis of the polyphosphate products, ADP and inorganic pyrophosphate. The latter reactions have been studied over the acidity range 1--5 M perchloric acid at 25 degrees C while the more complex problem of the hydrolysis of ATP has been followed at a single acidity (3 M perchloric acid). The positions of bond fission have been determined for both ATP and ADP.
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PMID:Mechanisms of hydrolysis of adenosine 5'-triphosphate, adenosine 5'-diphosphate, and inorganic pyrophosphate in aqueous perchloric acid. 627 Nov 94

1. The effect of heat-stable enterotoxin (ST) of Escherichia coli, cholera toxin (CT), and theophylline (a phosphodiesterase inhibitor) on ion and water transport was studied with an in vivo isolated loop system of the pig colon.2. All three agents abolished net Na absorption as a result of a decrease in the lumen to blood Na flux alone. With all three agents, net Cl absorption was reduced, but not abolished, and net HCO(3) secretion was elicited. Luminal p(CO2) was reduced with CT and theophylline from that observed in normal Ringer alone.3. Theophylline resulted in a prompt and sustained increase in both cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP) levels in colonic mucosa studied in vitro. ST selectively elevated cyclic GMP, whereas CT selectively elevated cyclic AMP. These responses paralleled the time course and magnitude of response of the transepithelial electrical potential difference (psi(LB)) measured in vivo.4. Ion replacement studies in the presence or absence of theophylline showed that in the absence of Na, Cl absorption was slightly reduced and HCO(3) secretion was elicited; no further additive effects of theophylline in the absence of luminal Na were observed. In the absence of luminal Cl, net Na absorption was abolished and HCO(3) was absorbed; theophylline resulted in significant net Na and HCO(3) secretion. Theophylline also increased psi(LB) in the absence of either luminal Na or Cl.5. Results suggest that in the presence of theophylline or enterotoxin, the coupled Na-H and Cl-HCO(3) exchange processes that are normally responsible for at least half of the net NaCl absorption by this tissue are interrupted. Active HCO(3) secretion is observed and Cl absorption under these conditions can be entirely explained as a consequence of psi(LB). Thus, these studies indicate that the colon may participate in the production of diarrhoea of enterotoxigenic origin. They also suggest an important functional role of cyclic nucleotides in controlling the acidity and volume of colonic contents.
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PMID:Effect of Escherichia coli heat-stable enterotoxin, cholera toxin and theophylline on ion transport in porcine colon. 627 79

The concentration dependence of the chemical shifts of the protons H-2, H-8, H-10, H-11, and H-1' of 1,N6-ethenoadenosine 5'-monophosphate (epsilon-AMP2-) has been measured. The results are consistent with the isodesmic model of indefinite noncooperative stacking; the association constant, K = 2.5 +/- 0.3 M-1, is within experimental error identical to the value determined earlier for AMP2-,K = 2.1 +/- 0.4 M-1. The conditions for the potentiometric pH titrations, used to determine the acidity constants of H2(epsilon-AMP), H2(AMP), and H(UMP)- and the stability constants of the metal ion (M2+) complexes of the corresponding nucleoside 5'-monophosphates (NMP), were chosen so that the ligands were present in the monomeric form. The stabilities of Mg(epsilon-AMP) and Mg(AMP) are similar; however, the stabilities of the Mn2+, Cu2+ and Zn2+ complexes of epsilon-AMP2- are much larger (in the case of Cu2+ by a factor of 700) than those of AMP2-. This is due to the much larger metal ion affinity of the epsilon-adenosine moiety compared to that of the parent adenosine residue. As the uridine moiety does not participate in complex formation, the stability constants of M(UMP) have been used to evaluate the extent of macrochelation (i.e. the simultaneous coordination of M2+ to the base moiety and the phosphate group) in the epsilon-AMP and AMP complexes: the concentration of the macrochelated isomer is considerably larger for M(epsilon-AMP) than for M(AMP). A comparison with previous results for the complexes with ADP3- and ATP4- indicates the order, M(AMP)cl less than M(ADP)-cl greater than M(ATP)2-cl for the tendency to form macrochelates (cl). Due to the relatively high affinity of the epsilon-adenosine moiety towards Mn2+, Cu2+ and Zn2+, the phosphate-monoprotonated complexes M(H . epsilon-AMP)+ also become important; the corresponding complexes play only a minor role in the M2+/AMP systems. Intramolecular aromatic-ring stacking occurs in the ternary Cu(2,2'-bipyridyl)(NMP) complexes: about 80% of Cu(Bpy)(AMP) and Cu(Bpy)(epsilon-AMP) exist as the stacked isomer in aqueous solution; for the former system it has been shown in a previous X-ray study that the intramolecular ligand-ligand interaction occurs also in the solid state [Aoki, K. (1978) J. Am. Chem. Soc. 100, 7106]. Overall, the results emphasize that great care should be exercised in drawing conclusions based on studies of metal-ion-containing enzymic systems in which the natural adenine nucleotide cofactors have been replaced by the corresponding 1,N6-etheno derivatives.
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PMID:On the metal-ion coordinating properties of the 5'-monophosphates of 1, N6-ethenoadenosine (epsilon-AMP), adenosine and uridine. Comparison of the macrochelate formation in the complexes of epsilon-AMP, AMP, ADP and ATP. 632 Nov 71

Previous studies (Carr and Acott , 1984) indicate that bovine sperm are maintained in a quiescent state in the caudal epididymis (CE) by a pH-dependent inhibitory factor. Here, we have determined that the pH of bovine CE fluid and of CE semen is approximately 5.8, and that the motility of CE sperm in undiluted CE fluid increases as the pH is elevated. Therefore, the acidity of CE fluid may play a physiological role in the maintenance of sperm quiescence. The changes in sperm motility, in response to changes in the pH of CE fluid, are reversible and rapid. Dilution of CE fluid with buffers at either pH 5.5 or 7.6 produces a much slower initiation of motility. In buffer a significantly lower pH is required to inhibit sperm motility than is required in CE fluid. The apparent pKs for inhibition are 5.3 in buffer and 6.6 in CE fluid. However, the motility of sperm in buffers that contain lactate, shows a pH dependence similar to sperm in CE fluid. That is, lactate inactivates sperm in buffer at pH 5.5 but not at pH 7.6. Lactate, and several other permeant weak acids, have previously been shown to reduce the intracellular pH of bovine sperm and many other types of cells. We show that these permeant weak acids, but not impermeant weak acids, reversibly reduce CE sperm motility in buffer at pH 5.5 but not at pH 7.6. Weak bases, which have previously been shown to elevate intracellular pH, initiate sperm motility in CE fluid. These results suggest that intracellular pH can regulate CE sperm motility and may be the intracellular messenger for the pH-dependent quiescence factor. Although sperm cyclic AMP levels have been previously correlated with motility stimulation, cyclic AMP levels do not change when the pH of CE fluid is elevated, even though full motility is initiated.
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PMID:Inhibition of bovine spermatozoa by caudal epididymal fluid: II. Interaction of pH and a quiescence factor. 632 37

A novel autophosphorylating protein kinase, autophosphorylating protein kinase 500, independent of cyclic AMP, cyclic GMP, calcium, and calmodulin was purified from rat adrenocortical carcinoma 494 by ammonium sulfate fractionation followed by the chromatographic steps of DEAE-cellulose, gel filtration, cyclic AMP-epoxy Sepharose, and phosphocellulose. Sometimes two additional chromatographic purification steps of chromatofocusing and gel filtration were necessary for complete purification. The enzyme was homogeneous as evidenced by one- and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sucrose density sedimentation studies indicated that Mr of the enzyme was 490,000, while ultracentrifugal analysis demonstrated a value of 481,400 (+/-7%). The protein was composed of two identical subunits each with Mr = 250,000. The enzyme molecule was slightly asymmetric with frictional and sedimentation coefficients of 1.28 and 18.20, respectively, and a Stokes radius of 66 A. Isoelectric focusing electrophoresis revealed a single peak with pI 4.6, indicating acidity of the protein. The enzyme self phosphorylated one or more of its serine residues. The reaction utilized the terminal phosphate of ATP; GTP was inactive. Divalent cations (5 mM Mn2+ or 10 mM Mg2+) were essential for optimum activity. Autophosphorylating protein kinase 500 did not phosphorylate the commonly used exogenous substrates such as histones, casein, phosvitin, or protamine. Analysis of autophosphorylating protein kinase 500 with rabbit anti-autophosphorylating protein kinase 500 IgG by immunoelectrophoresis and crossed immune electrophoresis demonstrated single arcs of precipitation, confirming the biochemical demonstration of enzyme purification and homogeneity. Indirect immunofluorescence studies revealed an intracytoplasmic localization of the enzyme in cultured and freshly isolated adrenocortical carcinoma 494 cells. Both cell types revealed an intensity of perinuclear enzyme fluorescence, but an absence of the enzyme in the nuclei or nucleoli. The anti-autophosphorylating protein kinase 500 IgG blocked the self-catalyzed phosphorylation of autophosphorylating protein kinase 500, providing immunological support of the biochemical results that autophosphorylation is an intrinsic characteristic of the enzyme. When autophosphorylating protein kinase 500 was incubated with membrane-bound ribosomes, it phosphorylated a Mr = 31,000 protein. This phosphorylation was blocked by the anti-autophosphorylating protein kinase 500 IgG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rat adrenocortical carcinoma 494 autophosphorylating protein kinase, autophosphorylating protein kinase 500. Purification, biochemical and immunological characterization, and substrate specificity. 637 Oct 13

Past studies of norepinephrine-stimulated protein phosphorylation in intact C-6 glioma cells had identified a 58,000 molecular weight, 5.7 isoelectric point protein (58K-5.7) as a cyclic AMP-dependent phosphoprotein and had shown that 58K-5.7 was one of the most abundant proteins of the nuclear fraction. Initial experiments of present studies showed that the 58K-5.7 protein remained with the nuclear ghost, or matrix structure, after removal of chromatin. Based on the size, acidity, abundance, nonsolubilization by nonionic detergent and salt, and solubilization by urea, the hypothesis was advanced that the 58K-5.7 protein was the vimentin-type intermediate filament protein. The hypothesis was tested by two types of immunochemical experiments. Antisera against hamster vimentin reacted selectively with only the 58K-5.7 protein in polyacrylamide gels of urea-solubilized cellular residues (i.e., nonionic detergent and 0.6 M salt-insoluble material) as determined by immunoautoradiography. Antisera against the pure 58K-5.7 protein of C-6 cells bound selectively to a fibrous array of cellular material typical of vimentin filaments as determined by indirect immunofluorescence. It is concluded that the 58K-5.7 protein is vimentin.
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PMID:Vimentin: a phosphoprotein under hormonal regulation. 702 79


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