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Biomedical subjects

A M Lynch

Publications and source records attributed to A M Lynch.

42 records · Page 3Linked to original sources

Placental growth in rats exposed to carbon monoxide at selected stages of pregnancy.

Maternal hypoxemia has been associated with fetal-growth retardation and placental hypertrophy. Here, rats were exposed to carbon monoxide (CO), 100 ppm, at different stages of gestation to determine when during pregnancy placental hypertrophy can be elicited, whether hypertrophy is sustained when the stimulus is removed, and whether placental hypertrophy correlates with maintenance of normal fetal growth. Groups of rats (11-17 per group) were exposed to CO, throughout gestation, or over days 1-16, 4-12, 10-22 and 18-22, to cover significant periods of placental growth. Maternal carboxyhemoglobin levels were estimated to be in the order of 10-14%, but there was no effect on fetal survival. Fetal weights were significantly reduced by 8 and 6% in groups treated over days 1-22 and 10-22 of pregnancy, but not in those where treatment ceased before term, and surprisingly not in the group treated over days 18-22, the stage of maximal fetal growth. Placental weights were significantly increased by 11-13% in all groups in which carbon monoxide exposure was continued to term, but were unaffected in cases where treatment ceased before term. These results show that near term the placenta, when it is thought to normally reach the limit of its functional capacity, can hypertrophy in response to CO, and suggest that this response benefits the fetus presumably by improving oxygen transport.

Animals↗

Lactate alters plasma membrane potential, increases the concentration of cytosolic Ca2+ and stimulates the secretion of insulin by the hamster beta-cell line HIT-T15.

We have studied the effect of lactate on a number of intracellular events which may be important in controlling the secretion of insulin by the hamster beta-cell line HIT-T15. Using the fluorescent dye Oxonol V, as well as intracellular recording techniques to measure changes in membrane potential, we found that lactate, glucose, K+ and tolbutamide caused depolarization of HIT cells, while valinomycin resulted in hyperpolarization. Consistent with these findings was the observation that 10 mM lactate caused an increase of 69.0 +/- 18.4% (S.E.M., n = 6) in the level of free cytosolic Ca2+ within HIT cells (assessed by fluorescence of quin 2). This was probably due to influx of Ca2+ through voltage-sensitive calcium channels, since it was dependent upon the concentration of extracellular Ca2+ and inhibited by verapamil. Lactate also caused cytosolic acidification in HIT cells and increased the secretion of insulin. These findings are consistent with the view that the electrogenic efflux of lactate could be a determinant in the activation of HIT cells by lactate and possibly by glucose.

Acetates↗

A rapid method for the reconstitution of Na+-dependent neutral amino acid transport from bovine renal brush-border membranes.

1. A simple and rapid method for the reconstitution of Na+-dependent neutral amino acid transport activity from bovine renal brush border membranes is described. 2. The neutral detergent decanoyl-N-methylglucamide ('MEGA-10') was employed to solubilize the membrane protein. This obviated the necessity for a prolonged dialysis step. 3. The properties of amino acid transport in these vesicles were similar to those observed in native membranes. 4. This should be a useful procedure in the eventual identification and isolation of amino acid transport proteins.

Alanine↗

Evidence for a single common Na+-dependent transport system for alanine, glutamine, leucine and phenylalanine in brush-border membrane vesicles from bovine kidney.

The characteristics of the Na+-dependent transport of alanine, glutamine, leucine and phenylalanine were studied in bovine renal brush-border membrane vesicles. Inhibition of the transport of any one of these amino acids by any other was mutually competitive. The Ki value for the inhibition of alanine transport by leucine was similar to the Km for leucine transport; similar interrelationships existed for the other amino acids. Each amino acid was shown to exchange with each of the other amino acids across the membrane. From these and other results it is concluded that the Na+-dependent transport of these four amino acids is catalysed by a single common transport system.

Alanine↗

The acute effects of capsaicin on the cardiovascular system.

Arterial blood pressure and heart rate were recorded from male Wistar rats anaesthetized with urethane. Intravenous injection of capsaicin, 1 microgram, produced a reproducible triphasic effect on blood pressure, comprising an initial fall in blood pressure and heart rate, followed by a transient and then a sustained pressor response. The depressor response and bradycardia were abolished by vagal section. The transient pressor response was altered in shape by hexamethonium. Slow intravenous infusion of capsaicin, 50 micrograms over 12 min, produced only a sustained pressor response accompanied by tachycardia, which was resistant to hexamethonium but abolished by morphine and pithing. Responses to both 1 microgram injection and 50 micrograms infusion of capsaicin were unaffected by the SP antagonist, spantide, but were abolished by capsaicin pretreatment of the rats. Capsaicin induces complex effects on the cardiovascular system, the nature of which varies with the dose and speed of administration.

Animals↗

Glucose increases cytosolic calcium concentration and inositol lipid metabolism in HIT-T15 cells.

We have investigated the effects of glucose on cytosolic free calcium concentration in the insulin-secreting cell line HIT-T15. Addition of glucose (10 mM) caused a 20-75% increase in cytosolic [Ca2+] within 5 minutes compared to controls in the absence of glucose. A maximal increase in cytosolic [Ca2+] was obtained with 5 mM glucose. The magnitude of the response was markedly dependent upon the concentration of extracellular Ca2+, and the rise in cytosolic [Ca2+] was inhibited by verapamil. Cytosolic [Ca2+] was greatly increased by depolarization of the cells with KCl (50 mM), whereas carbamylcholine had no apparent effect. Glucose and KCl were also effective in stimulating insulin release from HIT cells, although carbamylcholine was again ineffective. The secretory response to glucose was also found to be directly related to the concentration of extracellular [Ca2+]. Glucose and KCl, but not carbamylcholine, were found to slightly enhance the production of [3H]-inositol trisphosphate in HIT cells pre-labelled with myo-[3H]-inositol, indicating a modest stimulation of inositol lipid hydrolysis.

Adenoma, Islet Cell↗