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Effect of hydrogen ion concentration on corticosteroid secretion.

The direct effects of changes in extracellular hydrogen ion (H+) concentration on corticosteroid secretion under basal and ACTH-stimulated conditions were studied in isolated, perfused canine adrenal glands. Changes in extracellular H+ concentration were produced by altering either PCO2 or [HCO-3] of the Krebs-bicarbonate perfusate. Alkalosis markedly inhibited ACTH-stimulated aldosterone secretion. Moreover, within the range of pH from 7.19 to 7.85, there was a positive correlation between H+ concentration and the fractional secretion of aldosterone but a negative correlation between H+ concentration and the fractional secretion of corticosterone and 18-hydroxycorticosterone in response to ACTH. In contrast, neither acidosis nor alkalosis had a significant, direct effect on basal or ACTH-stimulated cortisol secretion. We conclude that 1) H+ concentration modulates the stimulatory effect of ACTH on aldosterone secretion by a direct action on the adrenal cortex, 2) acid-base disturbances are specific to the zona glomerulosa of the canine adrenal gland, and 3) H+ concentration may influence events occurring late in the pathway for aldosterone biosynthesis.

18-Hydroxycorticosterone↗

Effect of hydrogen ion concentration on energy metabolism in pig platelets.

Respiration and glycolysis of pig platelets suspended in a dialyzed plasma were studied at various hydrogen ion concentrations. Respiration of platelets was high at acidic pH and decreased at physiological pH. This pH profile may not be attributed to properties of mitochondria, since the respiratory rate of mitochondria prepared from platelets was maximal at physiological pH. A low respiratory rate at physiological pH seemed to be attributable to depression of respiration by glycolysis, since the addition of glucose further depressed the rate. The Crabtree effect was more prominent at alkaline ph. glycolysis increased with an increase in the pH of the plasma, contrary to oxygen comsumption. The Pasteur effect was less prominent at alkaline pH. The effect of pH on lactate production by the cytosol fraction of platelets was similar to that of whole platelets. The glycolytic intermediate pattern showed that phosphofructolinase was the committed step. Both ATP concentration and ATP formation calculated from respiratory and glycolytic rates were constant at various pH values. These observations may indicate that the pH primarily affects platelet glycolysis at the phosphofructokinase step and the respiration is secondarily controlled by glycolysis.

Animals↗

Circular dichroism studies of substance P and its C-terminal sequences. CD spectra in aqueous solution and effects of hydrogen ion concentration.

CD spectra of substance P (SP) and its C-terminal partial sequences have been measured in diluted aqueous solution including variation of hydrogen ion concentration. In the far u.v. region there is an overlapping of the amide CD absorption by the CD of the phenylalanine residue aromatic side chains (217-220 nm). This complex CD absorption is reduced during changes from acidic to alkaline pH, especially in those cases where a phenylalanine residue is at the N-terminus of the peptide chain. These CD changes dependent on pH are due more to charge effects on the aromatic chromophores than to substantial conformational changes. However, solvation effects on the conformational features of SP peptides caused by the deprotonation of the amino groups have to be taken into account. CD and potentiometric titrations indicate that the N-terminal alpha-amino groups of the SP peptides in general are freely accessible to the solvent. Our studies did not give any evidence of the occurrence of ordered structures of SP peptides in diluted aqueous solution.

Amino Acid Sequence↗

Hydrogen ion concentration and oxygen uptake in an isolated canine hindlimb.

Oxygen utilization (VO2) and lactate production by an isolated perfused canine hindlimb was evaluated at various hydrogen ion concentrations. A membrane lung perfusion system was established such that blood flow and temperature could be fixed at normal levels. Oxygen, nitrogen, and carbon dioxide (CO2) gas flows to the membrane lung were independently regulated to provide a fixed arterial oxygen content (CaO2). By changing CO2 flow, the pH of the arterial blood was varied between 6.9 and 7.6 at 10-min intervals. The mean O2 delivery (CaO2 X blood flow) was between 16.3 ML O2/min and 20.5 ml O2/min. Standard error of the mean in each dog, however, was less than 0.4 ml O2/min. VO2 was linearly related to the pH of the perfusing blood: VO2% = 100.1 pH - 643 (r = 0.866). Oxygen consumption was inversely related to PCO2: VO2% = -0.62 PCO2 + 124, but the correlation was less good (r = 0.729). Lactate production was linearly related to the pH of the perfusing blood (above a pH of 7.4): lactate produced = 22.5 pH - 162.5 (r = 0.75). At a pH below 7.4, lactate was not produced. Oxygen consumption of skeletal muscle appears critically dependent on extracellular fluid pH. A change in pH of 0.1 alters VO2 almost exactly 10%. Alkalosis is a potent stimulus to lactic acid production by skeletal muscle.

Animals↗

Significance of hydrogen ion concentration on the dissolution of mercury from dental amalgam.

The potential risks of mercury dissolution from dental amalgam have long been recognized. This study examined the effect of hydrogen ion concentration on the release of mercury from two dental amalgams: an admixed high-copper amalgam and a new tin- and copper-free amalgam. Specimens of each type of amalgam were incubated citric acid buffer of pH 2.5 or pH 7.0. Results showed that, for both types of amalgam, specimens incubated at pH 2.5 released statistically significantly greater (P less than .0001) quantities of mercury than did specimens incubated at pH 7.0. Release of mercury from the tin- and copper-free amalgam was also statistically significantly greater (P less than .0001) than that of the higher-copper amalgam at both pH levels.

Citrates↗

Alterations in myocardial hydrogen ion concentration after temporary coronary occlusion: a sign of irreversible cell damage.

Alterations of hydrogen ion (H+) concentration in the myocardium of 60 cats were determined before release of coronary ligation of 30, 45, 60, 90 or 180 minutes' duration, or 5, 30 and 90 minutes after release of the occlusion, by pressing pH indicator paper on unfixed frozen heart sections. The H+ concentration had clearly increased (pH less than 6.0) in a transmural extension in the left ventricle before release of the coronary ligature. This elevated H+ concentration persisted some time in the subendocardial region despite release of the coronary occlusion, thus proving that the so-called no reflow phenomenon exists in involved myocardium after temporary coronary occlusion. A diminished H+ concentration (pH 7.4) was found in the border zone between the acid-reacting area and the normal muscle when the coronary occlusion lasted 180 minutes before release of the ligature or 30 minutes after release of the occlusion when the previous period of temporary occlusion had been longer than 30 minutes. Although areas manifesting an acid reaction vanished or diminished in size after release of coronary occlusion, the extent of alkaline-reacting zones showed no reduction in size, and muscle cell necrosis developed in these alkaline-reacting areas. It is assumed therefore that an alkaline reaction of the myocardium is an early sign of irreversible muscle cell damage.

Animals↗

Effect of hydrogen ion concentration and buffer composition on ligand binding characteristics and polymerization of cow's milk folate binding protein.

The ligand binding and aggregation behavior of cow's milk folate binding protein depends on hydrogen ion concentration and buffer composition. At pH 5.0, the protein polymerizes in Tris-HCl subsequent to ligand binding. No polymerization occurs in acetate, and binding is markedly weaker in acetate or citrate buffers as compared to Tris-HCl. Polymerization of ligand-bound protein was far more pronounced at pH 7.4 as compared to pH 5.0 regardless of buffer composition. Binding affinity increased with decreasing concentration of protein both at pH 7.4 and 5.0. At pH 5.0 this effect seemed to level off at a protein concentration of 10(-6) M which is 100-1000 fold higher than at pH 7.4. The data can be interpreted in terms of complex models for ligand binding systems polymerizing both in the absence or presence of ligand (pH 7.4) as well as only subsequent to ligand binding (pH 5.0).

Animals↗

Effect of environmental hydrogen ion concentration on regulation of insulin receptors in cultured R3230AC mammary carcinoma cells.

Insulin binding and responsiveness in primary cultures of R3230AC rat mammary tumor cells were studied as a function of the hydrogen ion concentration of the culture medium. When insulin binding was assayed at pH 7.4, cultures that were maintained for a sufficient length of time in acidic medium demonstrated a significant increase in insulin receptor concentration compared to control cultures. The increase in insulin binding, which occurred as cultures approached confluency, was attributed to the increased acidity rather than nutrient depletion of the culture medium. In contrast, maximum binding was observed when the pH of the assay buffer was above 8.0, independent of the culture conditions. Binding of Concanavalin A, reflecting more generalized cell surface glycoproteins, decreased as cultures approached confluency, but was unaffected by the pH of either the culture medium or the assay buffer. The effect of pH on insulin responsiveness was studied. Insulin receptors generated by acidic culture conditions demonstrated insulin-induced down-regulation. Regardless of the pH environment, all cells demonstrated the same amount of insulin binding after exposure to 10(-6) M insulin. Under the in vitro conditions employed, cultured cells did not demonstrate a significant response to added insulin by alteration in growth, substrate transport, or incorporation of precursors into macromolecules, although the basal rates of these parameters were lower in cells maintained in acidic pH environments. The data presented indicate the necessity of considering the pH of the culture medium in studies of receptor regulation. It is possible that tumor cells, due to increased lactic acid production, may be especially prone to these changes.

3-O-Methylglucose↗