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Biomedical subjects

M J Berridge

Publications and source records attributed to M J Berridge.

At least 163 records · Page 9Linked to original sources

Ion-selective electrode studies on the effects of 5-hydroxytryptamine on the intracellular level of potassium in an insect salivary gland.

Potassium-sensitive microelectrodes were used to measure the intracellular level of potassium in Calliphora salivary glands. During stimulation with 1 X 10(-8) M 5-HT, the potassium concentration increased from a resting level of 133.2 to 139.0 mM. When the external concentration of potassium was reduced below 2mM there was a rapid loss of potassium which could be partially reversed by 5-HT. During 5-HT stimulation, the addition of ouabain had no effect on a number of parameters including the rate of fluid secretion, the ionic composition of the saliva and the intracellular level of potassium. The possibility that potassium enters the cells passively is discussed.

Animals↗

Studies on the mechanism of fluid secretion by isolated salivary glands of Calliphora.

1. Potassium is the major cation in the secretion of the salivary glands of Calliphora and is necessary for full secretory rates. 2. Other ions (rubidium and sodium) can support secretion in the absence of potassium. 39. During stimulation with 5-HT a Nernst plot of the basal membrane potential has a slope of 53 mV for a tenfold change in external potassium concentration and the slope at rest deviates from this over the range I-20 mM external potassium. 4. Hyperpolarization of the basal membrane by 5-HT is abolished if the chloride in the bathing medium is replaced by isethionate. 5. The diuretic agent amiloride inhibits fluid secretion by a mechanism which may include a reduction in calcium entry in addition to its recognized effect on sodium permeability. 6. A model is proposed in which fluid secretion is driven by the active transport of potassium across the apical membrane with chloride following passively.

Amiloride↗

A freeze-fracture study of adult Calliphora salivary glands.

A freeze-fracture study of adult Calliphora salivary glands has revealed a high density (approx. 4500/mu2) of intramembraneous particles (80-110 A) in both the apical and basal membranes. Most of the particles were associated with the A face. The density of the stalked surface particles which coat the cytoplasmic surface of the apical membrane. The possible significance of these particles in ion transport is discussed.

Animals↗

Membrane permeability changes during stimulation of isolated salivary glands of Calliphora by 5-hydroxytryptamine.

1. The membrane resistance of isolated salivary glands was found to decrease in response to 5-HT. The change in resistance was calcium-dependent. 2. The resistance change of the apical membrane was found to be much greater than the change in resistance of the basal membrane. 3. Potential responses under current-clamped conditions showed that one part of the biphasic response to 5-HT (attributed to an increase in chloride permeability) could be reversed and the other part (attributed to an increase in a potassium pump) could not. 4. These observations have been incorporated into a model which, on evaluation, predicts all of the observed potential changes during the action of 5-HT. It suggests that the potential responses reflect changes in the internal chloride concentration produced by the calcium-dependent increases in chloride permeability.

Animals↗

Stimulus-secretion coupling in an insect salivary gland: cell activation by elevated potassium concentrations.

1. Fluid secretion by isolated salivary glands was stimulated by elevating the external potassium concentration. 2. The stimulatory effect of potassium was dependent on external calcium and was potentiated by a subthreshold dose of 5-hydroxytryptamine (5-HT). 3. During the action of 120 mM potassium there was a large calciumdependent decrease in transepithelial resistance similar to that produced with 5-HT at normal potassium concentrations. 4. These results on Calliphora salivary glands are compared with other cases where cells are activated by high potassium. In most cases, the effect of high potassium is dependent upon calcium, suggesting that the latter plays a primary role in cell activation.

5-Hydroxytryptophan↗

Control of cell division: a unifying hypothesis.

A constant feature of the initiation of cell division in a number of different cells is a rise in the intracellular level of calcium. The importance of cyclic nucleotides may depend on the way they interact with calcium. Cyclic AMP is apparently not an essential regulator of cell division but through its ability to modulate the intracellular level of calcium this cyclic nucleotide can exert profound effects on cell growth. In some systems (liver and salivary glands) cyclic AMP seems to augment the calcium signal whereas in others (lymphocytes and fibroblasts) it opposes calcium and can thus inhibit cell division. A rise in the level of calcium may be responsible for the parallel increase in cyclic GMP level which is usually associated with the stimulus to divide. An appealing feature of this calcium hypothesis is that it can account for the growth characteristics revealed by fibroblasts in tissue culture or embryonic cells during development. In both cases there is an initial phase of exponential growth during which I have proposed that the high level of calcium at mitosis persists into early G1 to provide the signal for the next division. In order to account for the sudden cessation of cell division at confluency, or at a specific stage during development, it is necessary to postulate that there is something different about the final mitosis which sets it apart from earlier mitoses. It is proposed that as the cells leave the last mitosis the level of calcium falls much more rapidly than it did during preceeding mitoses perhaps as a result of a more rapid rise in the level of cyclic AMP. This rapid rise in cyclic AMP level may have a dual function. Not only will it lower the level of calcium thus preventing further division, but it may also stimulate differentiation. Many of the embryonic cells which differentiate into specialized cells (lymphocytes, liver, salivary gland) retain the ability to divide if provided with appropriate stimuli. Although the nature of these stimuli vary considerably, they all seem to act by elevating the intracellular level of calcium.

Animals↗

The nature of the binding between LSD and a 5-HT receptor: a possible explanation for hallucinogenic activity.

1 (+)-Lysergic acid diethylamide (LSD) mimicked 5-hydroxytryptamine (5-HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora.2 Unlike 5-HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing.3 Both 5-HT and tryptamine prevented LSD from acting on the glands.4 LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine).5 The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system.

Alkaloids↗

Role of calcium and adenosine-3':5'-cyclic monophosphate in controlling fly salivary gland secretion.

The action of 5-hydroxytryptamine (5-HT) on an insect salivary gland was associated with a rise in adenosine-3':5'-cyclic monophosphate (cAMP) concentration and an increase in calcium uptake. An increase in secretion induced either by 5-HT or exogenous cAMP required extracellular calcium. Both 5-HT and exogenous cAMP increased (45)Ca efflux from previously labeled glands, but only 5-HT caused an increase in calcium uptake. The transepithelial potential in this tissue became more negative after addition of 5-HT, but more positive after addition of cAMP. 5-HT and cAMP induced a more negative potential when calcium was removed from the medium. It was concluded that both calcium and cAMP serve as intracellular messengers when 5-HT acts upon fly salivary gland.

Animals↗