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Biomedical subjects

G W Kidder

Publications and source records attributed to G W Kidder.

At least 37 records · Page 2Linked to original sources
PubMed1980

Carbon monoxide insensitivity of gastric acid secretion.

By the use of hyperbaric conditions, it is possible to obtain high CO/O2 while maintaining O2 tension at a level that is not in itself inhibitory of acid secretion in the isolated frog gastric mucosa. Free solution CO/O2 of up to 10:1 only inhibit acid secretion about 20%, less than expected. Considerations of O2 diffusion into a respiring tissue bounded by unstirred layers predict a CO/O2 at the terminal oxidase ranging from 12 to 64 under various conditions and positions in the tissue, with predicted inhibitions between 55 and 86%. The inhibition observed is light reversible, affects potential difference and resistance in a consistent manner but is never very large. In the absence of O2, the CO-cytochrome alpha 3 complex can be demonstrated spectrophotometrically. Among other possible explanations for these observations, it is suggested that this tissue may contain an inhibitor-insensitive oxidase for a portion of the cytochrome system directly involved in acid secretion.

Animals↗
PubMed1979

Adenine aminohydrolase: occurrence and possible significance in trypanosomid flagellates.

Adenine aminohydrolase (EC 3.5.4.2) from four species of Leishmania and from Crithidia fasciculata was examined for specific activities, affinity for substrate (adenine), and stability to heat. All were found to be strongly and non-competitively inhibited by both coformycin and deoxycoformycin, two tight-binding inhibitors of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). Deoxycoformycin is the more potent inhibitor of the two. Neither inhibitor was active against the purine phosphoribosyltransferases. When deoxycoformycin was added to the defined growth medium containing hypoxanthine as the purine source, the growth of C. fasciculata was unaffected, but when adenine was the purine source for the organism, severe inhibition resulted. This implies that hypoxanthine is the obligatory base for nucleotide synthesis and that the adenine phosphoribosyltransferase (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7) is, in some manner,idenied access to exogenous substrate.

Adenosine Deaminase↗
PubMed1979

The purine phosphoribosyltransferases of Crithidia fasciculata.

The purine phosphoribosyltransferases of Crithidia fasciculata were identified and some of their properties described. The organism possesses three separate enzymes for the production of AMP, IMP, and GMP. The evidence for this comes from the observed differences in elution patterns from gel filtration columns, differences in heat sensitivity, and especially the clear separation of hypoxanthine phosphoribosyltransferase from guanine phosphoribosyltransferase by affinity chromatography on GMP-agarose. APRTase is activated most efficiently by Zn++, whereas HPRTase and GPRTase are activated most effectively by Co++. In no case did the product mononucleotides produce strong inhibition of the transferase activities.

Adenine Phosphoribosyltransferase↗
PubMed1978

Cytochromes and gastric acid secretion. A reevaluation of mucosal acidification experiments.

Using an improved spectrophotometer, we have reinvestigated the report (Hersey, S.J. (1974) Biochim. Biophys. Acta 344, 157--203) that acidification of the mucosal surface of frog gastric mucosa produces a crossover point between flavoprotein and cytochrome b, thus identifying a site of energy coupling between the cytochrome and H+ transport systems. While we find spectrophotometric changes upon addition of HCl to the mucosal solution, we find similar changes upon addition of NaCl without pH change, but no changes when the pH is lowered by substitution of H+ for Na+ at constant osmolality. We show that osmolality changes, with consequent alteration in tissue light scattering, are responsible for these effects. Further, we can show that the pH changes used do not inhibit acid secretion, and that one cannot do so without osmolality increase. We conclude that the imputed crossover point is not demonstrated, and that models based on its existence must be revised.

Animals↗
PubMed1978

Transport and accumulation of purine bases by Crithidia fasciculata.

The capacity for the rapid transport of purine bases by Crithidia fasciulata is found only in cells starved for purines. Cells grown in complete medium transport poorly. Rapid transport capability appears and then disappears during growth of purine-depleted cultures. This rapid transport appears to occur by a process of mediated diffusion. Two mechanisms are involved, one of low velocity and high affinity, the other of high velocity and low affinity. Accumulation of the bases within the cell occurs by their rapid conversion to ribonucleotides by phosphoribosyltransferases.

Adenine↗
PubMed1977

Inhibitory action of the adenine analog, 4-aminopyrazolo(3,4-d)pyrimidine, in Crithidia fasciculata.

The adenine analog 4-aminopyrazolo(3,4-d)pyrimidine inhibits the growth of the kinetoplastid (trypanosomatid) flagellate Crithidia fasciculata. This inhibition is partially overcome only by adenine (of a number of purines tested), with an inhibition index of 0.025. More effective reversal of inhibition is obtained with any of a number of naturally occurring pyrimidine compounds, up to a concentration of 0.18 mM. Higher concentrations of pyrimidines or addition of guanine, as well as adenine and uracil, to the medium increases inhibition. The analog (presumably as the ribonucleotide) was found not to be inhibitory to any enzyme of the pyrimidine biosynthetic pathway that could be tested. It is suggested that the analog competes with adenine for adenine phosphoribosyltransferase (AMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.7), is converted to a ribonucleotide, and is incorporated into nucleic acid.

Adenine↗
PubMed1976

Enzymes of the orotate biosynthetic pathway in Crithidia fasciculata.

A study of the enzymes of the orotate biosynthetic pathway in the kinetoplasid flagellate Crithidia fasciculata has revealed a number of differences between them and those of other organisms, either prokaryotic or eukaryotic. Carbamyl phosphate synthesis could not be demonstrated in cell-free extracts. However, the incorporation of both CO2 and the ureide carbon of citrulline into pyrimidines occurs in growing cells, the latter predominating over the former. The aspartate transcarbamylase of the flagellate has properties which are similar to those of this enzyme as it occurs in mammals rather than other microorganisms. Two enzymes, dihydroorotate synthetase and dihydroorotate hydrolase, are present, the former being responsible for the conversion of carbamylasparate to dihydroorotate. Dihydroorotate hydroxylase, a soluble enzyme requiring a reduced pteridine as a cofactor, converts dihydroorotate to orotate. The hydroxylase is inhibited by orotate, but not by pyrimidine or purine ribonucleotides. Thus orotate serves to control its own biosynthesis.

Amidohydrolases↗
PubMed1976

Sudden potential drop in bullfrog gastric mucosa.

The previously reported sudden potential drop (SPD), which occurs under anoxia in 10% CO2, has been further explored. We find several conditions necessary for this effect: 1) anoxia; 2) serosal pH less than 7.1;3) presence of chloride; and 4) a PD, either spontaneous or voltage clamped, which changes across the region of 10 mV, serosal positive. With the first three conditions satisfied, a reversible decrease in measured resistance can be produced at will by changing the clamp voltage. In the anoxic, low-resistance state, changes in K+ or C1- concentration give little change in voltage, showing that the increased conductivity is not selective for either ion. A model is proposed containing a shunt-resistance element whose resistance is a step function of PD. This model can mimic the responses of the tissue and provides a working model for the SPD.

Animals↗
PubMed1976

Effects of increased O2 and CO2 on acid secretion by dogfish gastric mucosa in vitro.

The gastric mucosa of the dogfish (Squalus acanthias), as usually prepared for in vitro chambered experiments, shows a secretory rate (JH) of about 2 mueq/cm2-h, but a potential difference (PD) of zero. Raising PCO2 from 0.05 to 0.1 atm increases JH by 40% and causes the development of a PD of about 2 mV, mucosal surface positive. Increasing PO2 from 0.9 to 1.9 atm in a hyperbaric chamber (at constant PCO2 = 0.1 atm) doubles JH and increases PD to 5 mV. Transepithelial resistance falls by 20% at high PO2. It appears that the dogfish gastric mucosa, like that of the frog, is rate limited by CO2 diffusion into the tissue from the usual 5% mixture and is also rate limited by the usual O2 levels (unlike the frog), presumably due to its thicker structure and higher O2 consumption. The mucosal-positive PD, which is reversed from all other mucosae studied, is readily explained by separate electrogenic H+ and Cl- pumps, but less readily by schemes embodying a neutral HCl pump. It is not yet known whether the hyperbaric conditions are sufficient to ensure O2 sufficiency.

Animals↗
PubMed1975

Electrophysiology of the frog gastric mucosa with sufficient CO2.

Changing from 5% CO2 in the serosal solution only to 10% CO2 on both sides doubles the acid secretory rate of the bullfrog stomach (as shown previously) and raises the transmural potential difference, although the short-circuit current is not changed. The secretory overshoot on reoxygenation after anaerobiosis, observed in 5% CO2, is virtually eliminated in 10% CO2, as predicted by the diffusion model which explains the secretory rate increase. It was found that the rate of rise of the secretory rate during anoxia was identical in the 2 conditions, which explains the increased secretory lag in 10% CO2 and suggests an interesting limitation on the rate with which acid secretion can be activated. During anoxia in 10% CO2, but not in 5% CO2, there occurs a sudden drop in PD to a slightly negative value associated with a fall in tissue resistance. This effect occurs under SCN-inhibition and thus seems unrelated to H+ transport per se. A working model is presented which can explain some of the events surrounding the sudden potential drop.

Animals↗
PubMed1975

Oxygenation of frog gastric mucosa in vitro.

We have recently shown that 5% CO2/95% O2 in the serosal bathing solution, with 100% O2 in the mucosal solution, results in CO2-diffusion limitation of acid secretion in bullfrog gastric mucosa. Changing to 10% CO2/90% 02 on both surfaces doubles the acid secretory rate. We calculate that, were the rate of oxygen consumption to increase significantly as a result of secretory stimulation, the tissue would now be oxygen limited. This prediction is tested by raising the P02 by increasing the total pressure in a hyperbaric chamber. Since no change in acid secretory rate or potential difference was observed upon changing from PO2 = 0.9 to PO2 = 1.9 atm, we conclude that the tissue is not O2 limited at normal pressure. Decreasing PO2 below 0.9 atm, by contrast, decreases the acid secretory rate and raises both PD and resistance. We infer that the rate of oxygen consumption did not rise significantly when acid secretion was increased by supplying sufficient CO2.

Animals↗