Phosphatidic acid mimicks the muscarinic action of acetylcholine in cultured bovine chromaffin cells

Ohsako, Shunji; Deguchi, Takao

doi:10.1016/0014-5793(83)80482-7

Cited by 28 publications

(13 citation statements)

References 25 publications

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“…4), whereas exogenously added phospholipase C was unable to do so. Furthermore, the addition of exogenous PA to CTLL-2 cells clearly shifted the dose-response curve of IL-2 to lower Although, PA has been shown to be a calcium ionophore for some cells [2S, [35][36][37], the calcium ionophore A23187 was unable to induceTcel1 proliferation, either alone or in the presence of low doses of IL-2. Furthermore, the addition of PA (even at 50 vg/ml) did not cause an increase in intracellular Ca2+, suggesting that PA activity is not merely due to an increase in the intracellular Ca2+ (data not shown).…”

Section: Induction Of T Cell Proliferation By Pamentioning

confidence: 99%

Regulation of interleukin‐2 responses by phosphatidic acid

1992

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Interleukin-2 (IL-2) plays a central role in the immune system by regulating the proliferation and differentiation of T lymphocytes. However, the molecular mechanism of the signal transduction through the IL-2 receptor is poorly understood. We have studied the role of phosphatidic acid (PA) on IL-2 signal transduction using cloned T lymphocytes. IL-2 stimulated a transient increase in the PA concentration in resting CTLL-2 cells prelabeled with [3H]palmitic acid. This effect was detected as early as 1 min after IL-2 addition and peaked at 5 min. IL-2 similarly increased phospholipase D activity in intact CTLL-2 cells, as inferred by phosphatidylethanol production. By contrast, IL-2 did not affect [3H]palmitic acid-labeled diacylglycerol levels. Furthermore, exogenous addition of several natural or synthetic PA to T cells mimicked IL-2 activity. Thus, PA were able to induce DNA synthesis on CTLL-2 cells, although this effect was only 10%-20% of that observed with IL-2. PA showed a synergistic effect with low doses of IL-2. In addition, PA was able to induce c-myc RNA transcription in CTLL-2 cells as well as IL-2 receptor (CD25) expression on the cell membrane with equal potency as saturating doses of IL-2. It is likely that IL-2-induced PA accumulation is a consequence of phospholipase D activation. This hypothesis is further supported by the fact that the addition of exogenous phospholipase D but not phosphatidylinositol-specific phospholipase C also reproduced the IL-2 or PA effects mentioned above. In summary, our results suggest a role of phospholipase D activation and PA formation as second messengers of IL-2 activity.

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Section: Induction Of T Cell Proliferation By Pamentioning

confidence: 99%

Regulation of interleukin‐2 responses by phosphatidic acid

1992

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“…Moreover, in bovine chromaffin cells and rat liver cells, an increase in the intracellular Ca2+ level may be effected by either muscarinic stimulation or calcium ionophore treatment, resulting in an eleva tion of cGMP content. One interpretation of this find ing is that an increase in guanylate cyclase activity takes place after increased uptake of Ca2+ [17,18]. Therefore, a Ca2+-mediated cell-activating process may be caused by an increase in cGMP content and the A/G ratio seems to be an indication of the hista mine release response.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Oxatomide on Intracellular Ca Mobilization, Ca Uptake and Histamine Release, Using Rat Peritoneal Mast Cells

Tasaka¹,

Akagi²,

Mio³

et al. 1987

Int Arch Allergy Immunol

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Oxatomide at concentrations of 0.01––10 μM inhibited not only an increase in ⁴⁵Ca uptake but also the intracellular Ca²⁺ release induced by compound 48/80 in rat peritoneal mast cells. At higher concentrations, ketotifen or other calcium antagonists caused similar inhibitory effects. However, the inhibitory effect of oxatomide on the ⁴⁵Ca uptake into rat neonatal heart cells was much weaker than that of verapamil. Through image processing of quin 2-stained mast cells, it was revealed that oxatomide inhibited Ca²⁺ release from the intracellular store. Although oxatomide alone did not affect cAMP and cGMP contents in sensitized guinea pig lung samples, the drug effectively prevented changes in the nucleotide contents evoked by antigen challenge. These results suggest that the inhibitory effect of oxatomide on histamine release may be caused by a combination of (1) prevention of Ca uptake, which is highly selective toward mast cells; (2) inhibition of Ca²⁺ release from the intracellular Ca store, and (3) elevation of the cAMP content in mast cells.

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“…It has been suggested that cholinergic agonists stimulate release of Ca from intracellular stores via the phosphatidyl inositol breakdown pathway. There is controversy as to whether this is due to muscarinic stimulation (Ohsako and Deguchi, 1983;Schneider, 1985, 1986;Forsberg et al, 1986) or both, nicotinic and muscarinic stimulation (Eberhard and Holz, 1987). These authors agree, however, that Ca release from internal stores is small in bovine chromaffin cells and not sufficient to evoke secretion.…”

Section: The Evidence For Cosecretion Of Calcium and Catecholaminementioning

confidence: 99%

“…Secretory vesicles, during exocytosis, fuse with the plasma membrane and their inner space becomes continuous with the extracellular space. Uptake of Ca into secretory vesicles and discharge by exocytosis as a pathway of Ca export has not been investigated in detail. In studies attempting to characterize the mechanism of the termination of catecholamine release, stimulated Ca export has been interpreted solely as Ca efflux across the plasma membrane (Ohsako and Deguchi, 1983;Wada et al, 1984;Morita et al, 1987).…”

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confidence: 99%

Calcium Is Released by Exocytosis Together with Catecholamines from Bovine Adrenal Medullary Cells

Grafenstein

Powis

1989

Journal of Neurochemistry

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We have tested the hypothesis that exocytosis is a possible export route for calcium from bovine adrenal medullary cells. After prelabelling cells in primary tissue culture with 45Ca, evoked 45Ca export and catecholamine secretion show the same time course, a similar fraction of the total pool of 45Ca and catecholamine is released, and the same concentrations of carbamylcholine or KCl are required for half-maximal triggered release. Increasing the osmolarity of the extracellular medium or treating the cells with botulinum toxin type D inhibits both evoked catecholamine secretion and 45Ca export to the same extent without inhibiting 45Ca influx. Incorporation of 45Ca into chromaffin granules is very slow, however, and incorporated 45Ca is not immediately releasable. 45Ca entering the cell during short-term stimulation is not found in the releasable pool during a second period of triggered secretion. Our data suggest that chromaffin granules are the largest pool of intracellular calcium in bovine adrenal medullary cells and that most of the calcium in chromaffin granules does not rapidly exchange with cytoplasmic Ca, but can be released directly by exocytosis. Exocytosis does not appear to play a major role in exporting Ca that enters the cell during short-term stimulation.

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Phosphatidic acid mimicks the muscarinic action of acetylcholine in cultured bovine chromaffin cells

Cited by 28 publications

References 25 publications

Regulation of interleukin‐2 responses by phosphatidic acid

Regulation of interleukin‐2 responses by phosphatidic acid

Inhibitory Effects of Oxatomide on Intracellular Ca Mobilization, Ca Uptake and Histamine Release, Using Rat Peritoneal Mast Cells

Calcium Is Released by Exocytosis Together with Catecholamines from Bovine Adrenal Medullary Cells

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