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Biomedical subjects

R J Huxtable

Publications and source records attributed to R J Huxtable.

At least 127 records · Page 7Linked to original sources
PubMed1982

Guanidinoethane sulfonate and the disposition of dietary taurine in the rat.

Guanidinoethane sulfonate, a transport antagonist of taurine in brain synaptosomes and isolated perfused hearts, causes profound and rapid depletion of tissue taurine levels when given to rats as a 1% solution. In tissues outside of the central nervous system, guanidinoethane sulfonate on average decreased by half the absolute amount of taurine obtained from the diet. However, the percent of taurine derived from the diet increased from an average of 36% to an average of 58%. In the brain, guanidinoethane sulfonate had little effect on the absolute amount of taurine obtained from the diet, but increased the percent contribution of diet from an average of 60% to an average of 80%. Guanidinoethane sulfonate had no effect on the tissue:serum ratio of radioactivity in brain, thymus, muscle or pancrease 24 hours after an injection of [3H]taurine. However, other tissues showed significant decreases in tissue:serum ratio, ranging from 67% of control in the small intestine to 36% of control in the liver. In its taurine-depleting action, therefore, guanidinoethane sulfonate discriminates between taurine derived from diet and taurine derived from biosynthesis. I conclude that the taurine-depleting action of guanidinoethane sulfonate is complex in mechanism, being a combination of inhibition of transport and interference with synthesis.

Animals↗
PubMed1982

Diet and biosynthesis as sources of taurine in the mouse.

The quantitative importance of diet versus biosynthesis as sources of taurine has been established in mice receiving dietary levels of 0.062% [3H]taurine and 0.74% [35S]methionine as sole sulfur-containing amino acids. After 15 days on diets radiolabeled with these levels of taurine and methionine, 16% of total-body taurine had been derived from diet and 24% from biosynthesis. By 30 days, these contributions had risen to 29% and 33%, respectively, and by 61 days to 46%. The half-life of turnover of taurine in the mouse was 18.6 days. These findings indicate that, like the rat and guinea pig, but unlike the cat and human, the mouse exhibits considerable biosynthetic capacity for taurine.

Animals↗
PubMed1982

Relative contribution of diet and biosynthesis to the taurine content of the adult rat.

The relative contribution of diet and biosynthesis to the taurine content of the rat has been determined quantitatively under various dietary conditions. Rats were maintained on diets containing [3H]taurine and/or [35S]methionine of known amounts and specific activities, and subsequently the specific activity of taurine in various tissues was determined. This approach gives a quantitative measure of how much taurine is biosynthesized versus how much is derived from the diet regardless of the biosynthetic route or site of biosynthesis in the animal. With no taurine in the diet, over an 87-day period, 54% of the taurine in the animal had been biosynthesized. This fell to 29% if taurine was present in the diet, and the contribution of dietary taurine to body pools rose to 58%. These changes in biosynthetic contributions were not accompanied by an alteration in the rate of biosynthesis but by an alteration in rate of excretion. When the amounts of biosynthesized taurine appearing in the urine over 63 days was added to the amounts found in the carcass, 3.1 mmol were found to be biosynthesized by animals receiving taurine in the diet as compared to 2.9 mmol in animals on a taurine-deficient diet. In any one experiment, the contribution of diet or biosynthesis is invariant from tissue to tissue indicating that the rate of exchange of taurine between tissues is faster than the rate of elimination of taurine from the body.

Animals↗
PubMed1981

Sources and turnover rates of taurine in nursing and weaned rat pups.

The quantitative importance of the molar as a source of taurine for neonatal rats has been examined by maintaining female rats on a diet containing 3H-taurine until they were uniformly labeled, and then mating them. Rats were kept on the 3H-taurine diet throughout pregnancy and lactation. The transfer of taurine from the mother to the pup both in utero and during nursing could thus be followed, and the quantity of taurine biosynthesized by the pup calculated. Pups were weaned at 21 days of age onto either a taurine-free diet or a diet containing 0.4% of non-radioactive taurine. The loss of 3H-taurine from various organs was followed. Whole body half-life of 3H-taurine was 11.4 days from rats fed the taurine-enriched diet and 15.0 days for rats on the taurine-free diet. Regardless of the diet, internal organs and the brain had faster rates of turnover that turnover from the muscle or from the whole animal. Both groups showed the same increase in total body taurine in the 4 weeks after weaning, indicating that young rats can biosynthesize considerable quantities of taurine.

Animals↗
PubMed1980

Differential effects of amrinone on contractility and taurine influx in rat and guinea pig hearts.

Amrinone (5-amino-3,4'-bipyridin-6(IH)-one) is a non-glycoside, non-catecholamine, positive inotropic agent with an unknown mechanism of action. In the Langendorff-perfused isolated guinea pig heart, we found that amrinone produced a maximum increase in contractile force of 33% at a concentration of 10 micrograms/ml (10.7 x 10(-5) M), without change in heart rate. Maximum response occurred within 2 min of initiating perfusion, and increased contractility persisted for several minutes of drug-free washout. Amrinone neither alleviated nor aggravated spontaneous arrhythmias. At the time of maximum inotropic response, amrinone produced no change in cyclic AMP levels. In contrast to the guinea pig, the Langendorff-perfused isolated rat heart responded with a decreased contractility when perfused with amrinone. Furthermore, whereas amrinone stimulated the influx of taurine in guinea pig hearts, taurine influx remained unaltered in rat hearts. This is the first case of stimulated taurine influx not being associated with an increase in cAMP concentrations. In the guinea pig heart, amrinone increased markedly the half life of exchange of intracellular calcium. It has been suggested that amrinone is positively inotropic because of a direct action on the contractile proteins. On the basis of our observations, we think it more likely to be due to the alterations in calcium flux caused by amrinone.

Aminopyridines↗
PubMed1980

The mechanism of the adrenergic stimulation of taurine influx in the heart.

The mechanism of isoproterenol-stimulated taurine uptake was examined in the perfused rat heart. Hearts were perfused by the Langendorff technique in a non-recirculating system, while heart rate and contractile force were determined continuously. Perfusion with inotropic concentrations of glucagon stimulated the uptake of [3H]taurine. If the positive inotropic response to isoproterenol was blocked with verapamil, a calcium antagonist, the uptake of taurine was still stimulated. This indicates that inotropy per se, or calcium influx are not involved in the modulation of taurine influx, but that influx rats is responding to cell cyclic AMP levels. The lack of effect of the positively inotropic ionophores monensin and A23187 and the negatively inotropic ionophore valinomycin is in agreement with this conclusion. Taurine decreased calcium binding to cardiac sarcolemma by 31% at 1 mM concentration and 80% at 5 mM.

Animals↗
PubMed1980

Sodium-dependent, high-affinity taurine transport into rat brain synaptosomes.

Taurine uptake into rat brain synaptosomal fractions appears to occur by two saturable transport processes and by bulk diffusion. The transport requires the presence of sodium ions. The dependence of the transport on temperature and cellular respiration implies that the uptake is an active process. The active process is specific for taurine and closely related amino acids. Brain regions differ in their ability to transport taurine. Uptake is not due to mitochondrial contamination of the synaptosomal fractions. However, glial contamination might partly contribute to the uptake. Kainic acid lesions of rat corpus striatum and cerebellum reduce taurine uptake implying that the uptake is, at least partly, into neurons.

Animals↗
PubMed1980

Physiological and experimental regulation of taurine content in the heart.

High concentrations of taurine are found in the heart and these are increased still further in congestive heart failure. It appears that taurine is largely derived by influx from the circulation, and this influx is stimulated by cyclic AMP, whereas influx of alpha-amino acids is unaffected. Influx occurs via a saturable transport system that has strict requirements for ligands. Other substances are transported by this system, including beta-alanine, hypotaurine, guanidoethyl sulfonate, and, to a lesser extent, guanidinopropionate; and these are competitive antagonists for taurine transport. Guanidinoethyl sulfonate, in vivo, markedly lowers taurine concentrations over the course of a few days in all tissues examined in the rat and mouse (but not in the guinea pig). The concentrations of other amino acids are unaffected. Guanidinoethyl sulfonate may prove to be a useful substance in the study of the biological role of taurine, in view of its ability to regulate taurine content in a number of species. Despite the numerous pharmacological actions of taurine, its physiological function in the heart remains problematic. One function appears to be the modulation of calcium movements. The inotropic actions of taurine and beta-adrenergic activation may be linked via the cyclic AMP-dependent regulation of taurine influx.

Amino Acids↗