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Biomedical subjects

T Godfraind

Publications and source records attributed to T Godfraind.

At least 163 records · Page 9Linked to original sources
PubMed1981

Differentiation of Ca2+ pumps linked to plasma membrane and endoplasmic reticulum in the microsomal fraction from intestinal smooth muscle.

ATP promotes 45Ca uptake by the microsomal fraction from the longitudinal smooth muscle of guinea-pig ileum and this uptake is stimulated by oxalate. As the microsomal fraction is made up of various subcellular entities, we examined the localization of the Ca2+-transport activity by density gradient centrifugation, taking advantage of the selective effect of digitonin (at low concentration) on the density of plasmalemmal elements. When the 45Ca-uptake activity was measured in the absence of oxalate, its behavior in subfractionation experiments closely paralleled that of the plasmalemmal marker 5'-nucleotidase. In contrast, the additional Ca2+-transport activity elicited by oxalate behaved like NADH-cytochrome c reductase, a putative endoplasmic reticulum marker. The endoplasmic reticulum vesicles constituted only a small part of the membranes in the microsomal fraction, which explains that their Ca2+-storage capacity was not detectable in the absence of Ca2+-trapping agent. Low digitonin concentrations selectively increased the Ca2+ permeability of the plasmalemmal vesicles. The two Ca2+-transport activities were further differentiated by their distinct sensitivity of K+, vanadate and calmodulin. In this respect, the oxalate-insensitive and oxalate-stimulated Ca2+-transport systems resembled, respectively, the sarcolemmal and sarcoplasmic reticulum Ca2+ pumps in cardiac and skeletal muscle, in accordance with the subcellular locations established by density gradient centrifugation.

Animals↗
PubMed1981

A calmodulin-stimulated Ca2+ pump in rat aorta plasma membranes.

An ATP-driven Ca2+-transport system has been characterized in a microsomal fraction from rat aorta. Calmodulin enhanced 2.5-fold 45Ca accumulation by EGTA-treated microsomes incubated with 10 microM Ca2+ (in the absence of oxalate) by increasing markedly the apparent affinity of the transport system for Ca2+. The ionophore A23187 induced a rapid release of the sequestered 45Ca. The vesicles that took up 45Ca were distributed like plasmalemmal marker enzymes when the microsomal fraction was subfractionated by density gradient centrifugation. In particular, these vesicles were markedly shifted towards higher equilibrium densities after addition to the microsomes of 0.2 mg digitonin/mg protein before isopycnic centrifugation. We conclude that the calmodulin-stimulated Ca2+ pump associated with the microsomal fraction is located in plasmalemmal elements.

Animals↗
PubMed1981

Mechanisms of action of calcium entry blockers.

This review is focused on experimental observations that permit conclusions about the mechanism of action of calcium entry blockers. It is shown that studies on the blockade of contraction (or relaxation) of depolarized smooth muscle must be confirmed by direct estimates of calcium fluxes. Superimposition of dose-inhibition curves of contraction and 45Ca entry are a prerequisite for allowing a drug to be regarded as a specific calcium entry blocker. Among the main characteristics of such drugs are their tissue selectivity and use dependency in depolarized preparations. It is shown that one of these (flunarizine) interacts with binding sites located in the plasma membrane possibly associated with the calcium channels. The physiological role of calcium and possible therapeutic uses of calcium entry blockers are also summarized.

Animals↗
PubMed1980

Independence of the positive inotropic effect of ouabain from the inhibition of the heart Na+/K+ pump.

Isolated left atria from guinea pigs were stimulated at 3.3 Hz and bathed at 30 degrees C in Tyrode's solution containing 6 mM KCl. After equilibration, this solution was replaced by a low-K solution or by Tyrode's solution containing ouabain or dihydroouabain. These treatments evoked an increase in the contractility of the atria. The time to peak increase was about 30 min, and the inotropic effect was sustained for at least 40 min. After 30 min, 42K was added to the bathing solution in order to estimate the activity of the Na+/K+ pump. A linear relationship was observed between the degree of inhibition of the Na+/K+ pump and the increase in systolic tension. The regression line was the same for low-K solutions and dihydroouabain but not for ouabain. For a given degree of inhibition of the pump, ouabain evoked a higher increase in contractility. These findings indicate that inhibition of the Na+/K+ pump can be the only mechanism responsible for the positive inotropic effect of dihydroouabain but cannot be the sole mechanism for that of ouabain.

Animals↗
PubMed1980

Subcellular location of semicarbazide-sensitive amine oxidase in rat aorta.

With tyramine as substrate, a considerable part of the amine oxidase activity of rat aorta was inhibited by 0.1 mM semicarbazide. The residual activity was little affected by 1 mM semicarbazide. Oxidation of 5-hydroxytryptamine was not inhibited by 0.1 mM semicarbazide. The subcellular location of the semicarbazide-sensitive and semicarbazide-resistant amine oxidases was investigated by analytical density gradient centrifugation. The semicarbazide-resistant enzyme was identified with the mitochondrial monoamine oxidase, located in the outer envelope of mitochondria. The semicarbazide-sensitive amine oxidase was ascribed to the plasma membrane because it was distributed like 5'-nucleotidase and (oligomycin-insensitive) Mg2+-ATPase in various fractionation experiments, and markedly shifted by digitonin towards higher equilibrium densities in sucrose gradient.

Animals↗
PubMed1980

[Parathyroidectomy and calcium exchange in cardiovascular tissue in the SHR rat].

Previous work has shown that parathyroidectomy lessens hypertension if performed on young SHR (5-6 weeks of age). In this work, ionic changes (Na+, K+, Ca2+, Mg2+) were studied in heart and aorta during a chronic experimentation. In the heart, atria and ventricle, Ca2+ content was significantly diminished, 15 days after parathyroidectomy. Nevertheless after 8 months, this difference did not remain. A correlation between Ca2+ content and heart rate (lessened immediately after parathyroidectomy) is suggested. In the aorta, parathyroidectomy did not change Na+, K+, Ca2+ and Mg2+ content after 15 days. At the opposite Mg2+ content was significantly lessened after 8 months (-33 p. 100, p less than 0,001). Calcium content in the Lanthanum Resistant Fraction was also depressed significantly at this time. Variations in heart and aorta ionic contents are discussed in relation with hypertensive development.

Animals↗
PubMed1979

Inhibition by digoxin and SC4453 of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain.

SC4453 is a digoxin analogue with a pyridazine instead of a lactone ring on C17 beta. SC4453 was compared with digoxin with respect to inhibition of (Na+ + K+)-ATPase prepared from human heart, guinea-pig heart and guinea-pig brain. SC4453 was slightly less potent than digoxin but showed a similar sensitivity to K+. As for cardenolides, species differences in sensitivity to SC4453 were accounted for by differences in the rate of dissociation from the receptors. These observations confirm that the human heart is one of the tissues most sensitive to cardiac glycosides.

Animals↗