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Biomedical subjects

A Owen

Publications and source records attributed to A Owen.

At least 91 records · Page 5Linked to original sources
PubMed1984

Steroid-induced protein synthesis in giant-toad (Bufo marinus) urinary bladders. Correlation with natriferic activity.

We have identified a group of proteins (Mr approximately 70 000-80 000; pI approximately 5.5-6.0) in giant-toad (Bufo marinus) urinary bladders whose synthesis appears to be related to aldosterone-stimulated Na+ transport. Spironolactone, a specific mineralocorticoid antagonist in renal epithelia, inhibits the synthesis of these proteins as well as the natriferic effect of the hormone. Since a variety of other steroids (some of which are traditionally considered to be glucocorticoids) also stimulate Na+ transport in toad urinary bladders, we examined whether their natriferic activity was expressed in a fashion similar to that of aldosterone. Short-circuit current was used to measure Na+ transport, and epithelial-cell protein synthesis was detected with high-resolution two-dimensional polyacrylamide-gel electrophoresis and autoradiography. At a concentration of approximately 100 nM, dexamethasone, corticosterone and aldosterone were equinatriferic. Dexamethasone and aldosterone had identical dose-response curves, maximal and half-maximal activity being evident at concentrations of approximately 100 nM and 10 nM respectively. In contrast, at a concentration of approximately 10 nM, corticosterone had no effect on Na+ transport. The natriferic activities of these three steroids correlate with their known affinities for the putative mineralocorticoid receptor in toad urinary bladders. Natriferic concentrations of dexamethasone and corticosterone (140 nM) induced the synthesis of proteins with characteristics identical with those induced by aldosterone. Spironolactone, at an antagonist/agonist ratio of 2000:1, inhibited steroid-induced Na+ transport and the synthesis of these proteins. Thus it appears that all natriferic steroids share a common mechanism of action in toad urinary bladders. Natriferic activity can be correlated not only with relative steroid-receptor affinity but also with the induction of a specific group of epithelial-cell proteins.

Aldosterone↗
PubMed1983

Stimulus-secretion coupling of glucose-induced insulin release. LI. Divalent cations and ATPase activity in pancreatic islets.

Pancreatic islets can be viewed as a fuel-sensor organ. The amount of ATP used by the islet cells for the maintenance of adequate Ca2+ gradients across membranes is not known. An indirect approach to this issue consists in the measurement of Ca-ATPase activity. The kinetics of Ca-ATPase in islet homogenates yielded a Km for ATP close to 0.1 mM and two Km values for Ca2+ close to 0.13 and 4-6 microM, respectively. Within limits, the Ca-ATPase appeared as a distinct entity from Mg-ATPase. Several divalent cations, including Mg2+, inhibited the Ca-ATPase activity. Calmodulin also inhibited, significantly albeit modestly Ca-ATPase. The activity of the enzyme was increased at high pH or in the presence of bicarbonate. The reaction velocity at close-to-physiological concentrations of ATP, Ca2+ and H+ suggests that the consumption of ATP by the Ca-ATPase may account for a major fraction of the overall rate of ATP breakdown in intact islets.

Adenosine Triphosphatases↗
PubMed1983

Enzyme kinetics: a new procedure for data normalization.

A procedure is proposed to normalize enzymatic reaction velocities measured in separate experiments. After calculation of the Km and maximum velocity in each individual set of data, the velocities measured in each experiment are reanalyzed by regression analysis with the constraint that they yield a Km identical to the geometric mean of the individual Km's calculated originally. The V derived from this second analysis can be taken, in each experiment, as the reference value relative to which all reaction velocities are normalized. All normalized velocities are eventually pooled together to establish the final regression line. This relatively simple and reliable procedure overcomes several difficulties otherwise encountered when the kinetics of an enzymatic reaction are judged from data collected in separate experiments.

Enzymes↗
PubMed1982

The stimulus-secretion coupling of amino acid-induced insulin release. XI. Kinetics of deamination and transamination reactions.

L-Leucine and its nonmetabolized analogue, 2-aminobicyclo-[2,2,1]heptane-2-carboxylic acid (BCH) activate glutamate dehydrogenase in pancreatic islets, whether the reaction velocity is measured in the direction of glutamate synthesis or glutamate deamination. The rate of glutamate oxidative deamination is increased by ADP and inhibited by 2-ketoglutarate, NH4+ and GTP. The islet homogenate catalyzes the transamination between L-glutamate and either 2-ketoisocaproate or pyruvate, and between 2-ketoglutarate and L-leucine, L-aspartate, L-alanine, L-isoleucine, L-valine, L-norvaline or L-norleucine, but not b (+/-) BCH. The glutamate-aspartate transaminase is preferentially located in mitochondria relative to other transaminases. The parallel effects of L-leucine and BCH on glutamate dehydrogenase and their vastly different abilities to act as transamination partners may account for both analogies and discrepancies in the metabolic and functional responses of the islets to these two branched-chain amino acids.

Adenosine Diphosphate↗
PubMed1982

Mathematical modelling of cyclic AMP-Ca2+ interactions in pancreatic islets.

A mathematical model is proposed to account for the interactions between Ca2+ and cyclic AMP in the process of glucose-induced insulin release. This model allows simulation of experimental findings such as the glucose-induced accumulation of cyclic AMP in islet cells, the calcium dependency of the latter accumulation, the time course of 45Ca net uptake by the islets exposed to glucose and/or a phosphodiesterase inhibitor, the stimulation of insulin release by glucose, the suppression of such a release at low extracellular Ca2+ concentration and its amplification by phosphodiesterase inhibitors, the restoration of a significant secretory response to glucose in islets deprived of Ca2+ but exposed to a phosphodiesterase inhibitor, and the usual relationship between 45Ca net uptake and insulin release. All these data refer to studies performed over a 90-min incubation. The model is not suitable, however, to simulate the rapid response of the islet cells during the first few minutes that follow a change in the environment of the islets.

1-Methyl-3-isobutylxanthine↗
PubMed1977

Falling amniotic fluid palmitates in diabetic pregnancies.

Palmitic acid levels were measured in samples of amniotic fluid obtained from 15 patients with diabetes. Seven patients had palmitate values which decreased at some time in pregnancy but only one of the infants developed respiratory distress. Eight of the 15 patients had final amniotic fluid palmitate values which were greater than 0.07 mmol/l and one infant developed respiratory distress. The other seven patients had final amniotic fluid palmitate values of 0.07 mmol/l or less and one of the infants developed respiratory distress. The significance of falling amniotic fluid palmitate values is discussed.

Amniotic Fluid↗
PubMed1975

A comparison of the effects of ouabain and 2-deoxy-D-glucose on the thermodynamic variables of the frog skin.

Previous studies support the validity of a linear thermodynamic formalism relating the rates of active Na-+ transport and oxygen consumption Jr to the electrical potential difference delta-psi and the affinity A (negative free energy) of the metabolic driving reaction. The formulation was further tested in paired control and experimental hemiskins by the use of two inhibitors of Na-+ transport. Ouabain, a specific inhibitor of the Na-+ pump, might be expected to diminish the dependence of Jr on delta-psi without affecting A, whereas 2-deoxy-D-glucose, a competitive inhibitor of glucose metabolism should be expected to diminish A. Both inhibitors were used at concentrations adequate to depress Na-+ transport (i.e. short-circuit current Io) to some 50% of control level. Measurements were made of Io and dJr/d(delat-psi), and the apparent value of the affinity Aapp was calculated according to the thermodynamic formulation. Ouabain depressed minus dJr/d(delta-psi) without affecting Aapp whereas 2-deoxy-D-glucose depressed Aapp without affecting minus dJr/d(delta-psi). The demonstration of these effects indicated the utility of the formalism.

Animals↗
PubMedDate not supplied

A case of voluminous diarrhoea with hypokalaemic acidosis.

We describe a patient presenting with voluminous diarrhoea, hypokalaemic acidosis and hypercalcaemia who was found to have a vasoactive intestinal polypeptide-producing tumour. His diarrhoea was initially mild and intermittent requiring no medical attention.

Acidosis↗
PubMedDate not supplied

Mathematical modelling of stimulus-secretion coupling in the pancreatic B-cell. V. Threshold phenomenon for the response to cyclic AMP.

Recent experimental data suggest that a rise in cyclic AMP content of pancreatic islet cells may have little effect upon cytosolic Ca2+ activity. Hence, a mathematical model for stimulus-secretion coupling was designed in which cyclic AMP fails to affect Ca2+ movements in the islet cells, but augments the responsiveness to cytosolic Ca2+ of the effector system for insulin release. Provided that the latter effect of cyclic AMP becomes operative only when the nucleotide concentration exceeds a critical threshold value, the mathematical model was found suitable to predict the dynamics of both insulin release and 45Ca fluxes in islets deprived of or exposed to D-glucose, Ca2+ and a phosphodiesterase inhibitor.

Animals↗