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Biomedical subjects

G Powis

Publications and source records attributed to G Powis.

At least 235 records · Page 13Linked to original sources
PubMed1974

An uptake mechanism for L-noradrenaline in the cat spleen, associated with the nerves but distinct from uptake.

1. The characteristics of the uptake of [(3)H]L-noradrenaline from 1 mug pulses injected close arterially to the isolated blood perfused cat spleen are described.2. The spleen took up 355.0+/-16.0 ng from a first pulse and 321.1+/-43.6 ng from a second.3. Uptake from a second pulse was 254.0+/-30.3 ng in the presence of the Uptake(1) inhibitor desmethylimipramine (DMI) (3.3 x 10(-5)M) and the Uptake(2) inhibitor 17-beta-oestradiol (17beta0) (1.8 x 10(-4)M).4. Uptake from small 10 ng pulses was also insensitive to DMI and 17beta0.5. Uptake from pulses was abolished by surgical denervation of the spleen, or pre-treatment with phenoxybenzamine (PBA) (8.8 x 10(-5)M).6. The pulse uptake process was impaired by omission of red cells from the perfusate.7. Stimulation of the splenic nerves at 3Hz halved the pulse uptake.8. Uptake from infusion in the presence of DMI and 17beta0 occurred only during the first few minutes of the infusion.9. It is concluded that an uptake process for L-noradrenaline distinct from Uptakes(1) and (2) is present in the spleen and this might be important physiologically.

Animals↗
PubMed1973

The accumulation and metabolism of (-)-noradrenaline by cells in culture.

1. Cultured bovine embryonic tracheal cells, EbTr (NBL-4) possess a process for the intracellular accumulation of (-)-noradrenaline with the characteristics generally ascribed to extraneuronal uptake by cardiac and smooth muscle cells in the body. It has a K(m) of 2.6 x 10(-4)M.2. The accumulation process is inhibited competitively by normetanephrine, but only at relatively high concentrations, IC50=2.1 x 10(-4)M. Inhibition also occurs with 17-beta-oestradiol, IC50=1.3 x 10(-5)M.3. The noradrenaline metabolites, 3,4-dihydroxy-mandelic acid and 3,4-dihydroxy-phenylglycol potentiate accumulation and reduce intracellular levels of normetanephrine in a similar manner to known inhibitors of catechol-O-methyl transferase.4. It is suggested that intracellular, rather than extracellular, normetanephrine may exert feedback inhibition upon noradrenaline accumulation by combining with the transport process at the inner surface of the cell membrane.

Animals↗
PubMed1973

The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen.

1. Twenty minutes after the addition of pargyline (5 x 10(-4)M) to blood perfusing the isolated spleen of the cat, the overflow of transmitter resulting from stimulation of the sympathetic nerves increased 2.3-3-fold. Lower doses of pargyline did not significantly affect overflow.2. Monoamine oxidase activity, measured with either radioactively labelled tyramine or noradrenaline as substrate, was almost completely inhibited by doses of pargyline in the range of 10(-4)M to 5 x 10(-4)M. Inhibition of enzyme activity was not correlated with the effect on overflow. Pargyline had only a slight inhibitory effect on catechol-O-methyl transferase.3. Uptake of a 1 mug injection (pulse) of labelled noradrenaline, following pargyline (5 x 10(-4)M), was increased to 199.1% of that found in control experiments.4. Pargyline significantly reduced the vascular responses to nerve stimulation but had no significant effect on capsular responses.5. The inhibitor had no effect on resting overflow of labelled noradrenaline from the spleen but doubled the overflow of labelled noradrenaline following nerve stimulation.6. It is suggested that the effect of pargyline on overflow is due to increased release of transmitter during nerve stimulation.7. The possible clinical significance of these findings is discussed.

Animals↗
PubMed1973

Binding of catecholamines to connective tissue and the effect upon the responses of blood vessels to noradrenaline and to nerve stimulation.

1. Quantitative estimates have been made of the binding of catecholamines to purified collagen and elastin, and the factors influencing this binding have been investigated.2. Collagen shows no specificity towards the binding of either the (-)- or (+)-isomer of adrenaline or noradrenaline, at low concentrations. Elastin binds the (-)-isomer of adrenaline and noradrenaline to twice the extent of the (+)-isomer.3. Tetracyclines inhibit the binding of catecholamines to collagen and elastin. Oxytetracycline 10(-4)M produces a maximum inhibition of the binding of (-)-noradrenaline to collagen of 68.4%.4. The responses of perfused blood vessels to the administration of pulses of catecholamines or to adrenergic nerve stimulation have been measured.5. Oxytetracycline (10(-4)M) potentiates the amplitude of the response of the rabbit ear artery to noradrenaline and to nerve stimulation, ten- and sixfold respectively.6. Those preparations with a high content of collagen and elastic tissue, the rabbit ear artery and the rat tail, are more susceptible to the potentiating effects of oxytetracycline than one with a low content, the rat anococcygeus.7. The results of the study suggest that in tissues with a high content of collagen and elastin, binding to extracellular sites is the major mechanism for terminating the response to noradrenaline or to adrenergic nerve stimulation.

Animals↗
PubMed1971

Some properties of a preparation of rat colon perfused in vitro through the vascular bed.

1. A technique is described for the perfusion of the isolated colon of the rat, involving the infusion of an appropriate fluid through both the inferior and the superior mesenteric arteries. During neither the preparation nor the subsequent perfusion is the colon without an adequate supply of oxygen. The preparation remains histologically intact and metabolically viable and is capable of actively transporting ions for up to 5 hr.2. The addition of at least 3 g albumin/100 ml. perfusate is necessary to prevent the formation of large quantities of serosal exudate. With erythrocytes added to the vascular perfusate the preparation appears to be adequately oxygenated as judged by measurements of the rate of glycolysis. The mean rate of oxygen utilization over 4 hr is 9.2 +/- 0.3 (4) mumole. hr(-1).g(-1) fat free dry weight.3. Ion transport rates approaching those found in vivo are found only after the administration of an antihistamine substance to the colon donor rat before operation. In the absence of an antihistamine substance there appears to be an ultrafiltration of the plasma fluid into the lumen.4. Vasodilatory substances accumulate in the recycled perfusate. In a ;single pass' perfusion, the transport capacity of the preparation decreases at high perfusion pressures. It is suggested that this is due to some form of autoregulation whereby perfusate is shunted away from the epithelium into deeper layers as the pressure is increased.5. With CO(2) absent from the vascular infusate there is an increase in the net lumen to blood flux of total CO(2). This increased flux is accompanied by an equivalent amount of cation, comprising Na(+) and K(+) in the ratio of 12:1.6. The presence of ammonium in the lumen, a physiological constituent of the contents of rat distal colon in vivo, has a marked inhibitory effect upon the secretion of CO(2) into the contents of the lumen of the colon.

Animals↗
PubMedDate not supplied

Signalling pathways as targets for anticancer drug development.

Intracellular signalling pathways mediating the effects of oncogenes on cell growth and transformation offer novel targets for the development of anticancer drugs. With this approach, it may be sufficient to target a component of the signalling pathway activated by the oncogene rather than the oncogene product itself. In this review, the abilities of some antiproliferative drugs to inhibit signalling targets are considered. There are some anticancer drugs already in clinical trial that may act by inhibiting signalling targets, as well as drugs in preclinical development. Some problems that may be encountered in developing this new class of anticancer drugs are discussed.

Antineoplastic Agents↗