Search PubMed⌕ Search

Biomedical subjects

T J Rink

Publications and source records attributed to T J Rink.

114 records · Page 7Linked to original sources
PubMed1975

Catecholamine release from bovine adrenal medulla in response to maintained depolarization.

Prolonged exposure of venous-perfused bovine adrenal glands to high K in the presence of external Ca produces a transient increase in catecholamine output that reaches a maximum after about 1 min and then declines with a half-time of about 1-2 min. 2. The time course of the transient secretory response to high K does not depend appreciably on the total catecholamine output which indicates that depletion of releasable catecholamine is unlikely to be responsible for the transient nature of the response. 3. Application of 3-6 mM-Ba stimulates secretion from a gland after many minutes exposure to high K, when catecholamine output has declined close to resting levels. This provides further evidence that depletion does not play a major role in the transient response and shows that maintained depolarization does not inhibit the secretory mechanism. 4. Exposure to high K solutions in which Ca has been replaced isomotically by Mg does not evoke any catecholamine output. Subsequent application of Ca always elicits some secretion although the size of this response to added Ca declines rapidly during exposure to Ca-free, high K solutions. The failure of the secretory response in these experiments is more rapid, and earlier in onset than the declining phase of the normal secretory response evoked in the presence of calcium. 5. Pre-treatment with Ca-free solutions of intermediate K content reduces the response to subsequent simultaneous application of high K and Ca. There is a roughly sigmoidal relation between the reduction in response and the logarithm of the K concentration used for pre-treatment. 6. Thin slices of bovine adrenal medulla show qualitatively similar responses on exposure to high K. Examination of the flourescent signal from slices dyed with the potential-sensitive dye DiS-C(3)-(5) suggests that maintained exposure to high K produces a stable depolarization. 7. The most likely explanation for these results is that K-depolarization first activates and subsequently inactivates a potential-sensitive Ca permeability channel. This inactivation is time and possibly potential dependent. 8. The effect of high K on calcium movements in medullary slices was examined. Exposure to 72 mM-K increases (45)Ca uptake, the increase being greatest during the first 10 min. The efflux of Ca is also increased on exposure to high K in the presence of Ca. The net Ca uptake in 72 mM-K is smaller than the tracer uptake of Ca. These findings indicate that K depolarization stimulates a Ca-Ca exchange process. They are also consistent with, but do not offer strong positive support for, the idea that K-depolarization first activates and subsequently inactivates Ca entry. 9. It is suggested that Ca inactivation might play a role in the modulation of neurosecretion and neurotransmitter release by changes in membrane potential.

Adrenal Medulla↗
PubMedDate not supplied

Diacylglycerol and phorbol ester stimulate secretion without raising cytoplasmic free calcium in human platelets.

An increase in cytoplasmic free calcium, [Ca2+]i, is thought to be the trigger for secretory exocytosis in many cells. In blood platelets, large rises in [Ca2+]i can cause secretion and calcium has been regarded as the final common activator not only for secretion but also for shape-change and aggregation. We have shown that while thrombin and platelet-activating factor (PAF) normally elevate [Ca2+]i, they can also stimulate shape-change and secretion even when the [Ca2+]i rise is suppressed. The present results strongly implicate diacylglycerol, produced by stimulus-dependent breakdown of phosphoinositide, in this calcium-independent activation. Exogenous diacylglycerol activates a protein kinase (C-kinase) in platelets as do PAF, thrombin and collagen. 12-O-tetradecanoyl phorbol-13-acetate (TPA) also activates C-kinase and is a potent stimulus for secretion and aggregation. It is shown here that the exogenous diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG) and TPA evoke similar secretion and aggregation without elevating [Ca2+]i above the basal level of 0.1 microM. The pattern of secretion resembles that produced by collagen and thrombin when [Ca2+]i remains at basal levels. Modest increases in [Ca2+]i, insufficient to stimulate secretion, markedly accelerate the responses to TPA and OAG.

Blood Platelets↗
PubMedDate not supplied

Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers?

Endothelial cells line the inner surface of blood vessels and act as the main barrier to the passage of cells and large molecules from the blood stream to the tissues. Recent interest in the part played by the endothelium in regulating vascular tone has focused on the synthesis and secretion of prostacyclin and an endothelium-derived relaxing factor. Endothelial cells respond to blood-borne agonist, but how the endothelium senses and responds to mechanical forces generated by the flow of blood under pressure is not known. Here we report patch-clamp recordings of ion channel activity from cell-attached membrane patches on aortic endothelial cells. In most of the patches examined, we observed unitary inward currents associated with the opening of a cation-selective channel (approximately 40 pS in standard saline). The channel is permeable to Ca2+ and its opening frequency increases when the membrane is stretched by applying suction through the patch electrode. The presence of mechanotransducing ion channels in endothelial cells may help explain how the endothelium mediates vascular responses to haemodynamic stresses.

Animals↗