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D H Jenkinson

Publications and source records attributed to D H Jenkinson.

45 records · Page 3Linked to original sources
PubMed1972

Effects of noradrenaline on potassium reflux, membrane potential and electrolyte levels in tissue slices prepared from guinea-pig liver.

1. Some effects of noradrenaline on potassium efflux, electrolyte levels, membrane potential and current distribution in guinea-pig liver slices have been examined.2. The slices (thickness ca. 300 mum) were prepared from the median lobe of the liver and incubated at 38 degrees C in a mammalian Ringer fluid containing 2 mM pyruvate. After an initial recovery period, the ionic composition of the tissue remained stable for several hours.3. The steady-state contents of sodium, potassium and chloride were 296, 266 and 272 m-equiv/kg dry tissue respectively. The inulin space was 29 ml./100 g wet tissue.4. Most if not all of the tissue potassium was exchangeable. The rate constant for (42)K efflux was 0.019 min(-1).5. Noradrenaline (1 muM) markedly increased the efflux of (42)K and within 2 min caused tissue potassium to fall by 8%. At the same time the sodium content rose.6. Traverses of the slices with micro-electrodes showed many negative-going deflexions of 30-40 mV in amplitude. The evidence suggests that these correspond to the membrane potentials of the parenchymal cells.7. Noradrenaline (1 muM) caused a reversible hyperpolarization of about 10 mV. The response became larger on replacing external chloride by isethionate or methylsulphate, but was little affected by a reduction in external potassium.8. After slices had been bathed in potassium and chloride-free solutions for several min, restoration of external potassium caused the membrane potential to increase by up to 10 mV. This hyperpolarization, but not that caused by noradrenaline, was abolished by ouabain.9. Noradrenaline reduced the amplitude and quickened the time course of electrotonic potentials set up by current pulses from another microelectrode, suggesting that the membrane conductance had risen.10. Although certain mechanisms based on electrogenic active transport processes with unusual properties have not been excluded, the present findings are more simply explained by supposing that noradrenaline increases the potassium permeability of the parenchymal cell membrane.

Animals↗
PubMed1972

The receptors concerned in the actions of catecholamines on glucose release, membrane potential and ion movements in guinea-pig liver.

1. Experiments have been made to identify the kinds of receptors concerned in the actions of catecholamines in increasing potassium efflux, membrane potential and glucose release in tissue slices prepared from guinea-pig liver.2. Glucose release could be accelerated by activation of either of two distinct receptors, one of which resembles the alpha receptor of Ahlquist's classification, the other being beta-like. Thus both amidephrine and isoprenaline (sympathomimetic amines which selectively activate alpha and beta receptors respectively) elicited the response.3. The effect of isoprenaline on glucose release was inhibited by the beta blocking agent propranolol (1 muM) but not by the alpha blocker phentolamine (10 muM), whereas the converse held for amidephrine. However, the degree of antagonism observed with phentolamine was less than found in smooth muscle, suggesting that the alpha-like receptor in the liver may differ somewhat from that in other tissues, or be less accessible to the antagonist.4. Amidephrine, like noradrenaline, increased the efflux of (42)K from the slices and caused hyperpolarization, suggesting that the increase in potassium permeability underlying these responses is alpha-mediated. This conclusion was supported by the finding that the effect of amidephrine on membrane potential was inhibited by phentolamine but not propranolol (1 muM).5. In keeping with this interpretation, low concentrations (20-50 nM) of isoprenaline, although sufficient to activate the beta receptors (as judged by the effect on glucose release) had little effect on the ionic composition of the tissue, and caused only a small increase in (42)K efflux. Thus the ;ion movement' and ;glucose' responses could be largely dissociated.6. Larger concentrations (1-6 muM) of isoprenaline increased (42)K efflux to a greater extent, although the effect was always less than with the same concentration of noradrenaline.7. Activation of the beta-receptors caused a small and inconsistent hyperpolarization which became more pronounced and also more reproducible on replacing the chloride content of the bathing fluid by the larger anion isethionate.8. Although these results show that activation of either of two distinct adrenergic receptors in guinea-pig liver can cause the same end-response (e.g. an increase in glucose release, or, under some circumstances, hyperpolarization of the cell membrane), the underlying mechanisms cannot be assumed to be identical. This is discussed.

Adrenergic alpha-Agonists↗
PubMed1968

The effect of noradrenaline on the end-plate potential in twitch fibres of the frog.

1. The action of noradrenaline in increasing the amplitude of the end-plate potential (e.p.p.) has been studied in magnesium-blocked frog skeletal muscle.2. Noradrenaline (10(-5)M) increased the e.p.p. by about 20% without causing any comparable change in the amplitude of the miniature end-plate potentials (m.e.p.p.s). It was concluded that noradrenaline acts by potentiating the release of acetylcholine by the nerve impulse, rather than by increasing the sensitivity of the end-plate.3. In support of this, it was found that the increase in e.p.p. amplitude was associated with a reduction in the variability of successive e.p.p.s, as is to be expected if the quantal content of the e.p.p. became larger. Further, noradrenaline was without effect on the response to iontophoretically-applied acetylcholine, although it potentiated depolarizations elicited by acetylcholine applied for much longer periods in the bathing fluid.4. Noradrenaline increased the frequency of occurrence of m.e.p.p.s, and unusually large m.e.p.p.s. were occasionally observed.

Acetylcholine↗
PubMed1967

The effect of noradrenaline on the permeability of depolarized intestinal smooth muscle to inorganic ions.

1. Radio-isotopes have been used to study the effect of noradrenaline on the permeability of the taenia of the guinea-pig caecum to inorganic ions. The preparations were bathed at either 10 or 20 degrees C in solutions containing a high concentration of potassium, in order to depolarize the fibres and so avoid ionic movements secondary to changes in membrane potential.2. Under these conditions noradrenaline increased both inward and outward fluxes of potassium whilst having little effect on the exchange of chloride.3. No effect of noradrenaline on the uptake of sodium could be detected, whereas carbachol (carbamyl choline chloride), applied under identical conditions, caused a significant increase at a concentration chosen to match the effect of noradrenaline on potassium exchange.4. These results are discussed in relation to the hypothesis that an increase in potassium permeability contributes to the inhibitory actions of noradrenaline on intestinal smooth muscle.

Animals↗
PubMed1967

The role of alpha- and beta- adrenergic receptors in some actions of catecholamines on intestinal smooth muscle.

1. Experiments were carried out to determine the type of adrenergic receptor concerned in the action of noradrenaline in increasing the rate of exchange of potassium ions in the taenia of the guinea-pig caecum. The preparations were bathed in potassium-rich solutions in order to depolarize the muscle fibres and so eliminate changes in potassium flux secondary to alterations in membrane potential.2. Noradrenaline was more effective than isoprenaline in increasing both the influx and efflux of (42)K, suggesting that the alpha-receptors were involved. This action on potassium permeability was abolished by the alpha-blocking agent phentolamine (10(-7) g/ml.), the beta-blocking agent pronethalol (10(-7) g/ml.) being without effect.3. In contrast, isoprenaline was about 30 times more active than noradrenaline in inhibiting calcium contractures of the depolarized taenia, suggesting that here the beta-receptors were concerned. This was confirmed by showing that this action of noradrenaline was effectively antagonized by pronethalol, again at 10(-7) g/ml., but not by the same concentration of phentolamine.4. Carbachol contractures in quiescent preparations bathed in Krebs solution at 17 degrees C could be inhibited by both noradrenaline and isoprenaline. Noradrenaline was found to be more active under these conditions, and this action was antagonized by phentolamine (and piperoxane), but not by pronethalol, at the same concentrations as before.5. These findings confirm that the alpha- and beta-receptors are quite distinct in their actions. Nevertheless, under physiological conditions, both may contribute to the inhibitory actions of catecholamines on intestinal smooth muscle.

Animals↗