A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum

Tanaka, Chikako; Taniyama, Kohtaro; Kusunoki, Masato

doi:10.1016/0014-5793(84)80591-8

Cited by 76 publications

(29 citation statements)

References 27 publications

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“…From these results, we suggested an important role of 5-lipoxy genase metabolites in the release of acetylcholine. TPA was reported to increase electrical field stimulation or Ca2+ ionophore-induced acetylcholine release from the myenteric plexus of guinea pig ileum (10). In the present study, PDBu also increased spontaneous and electrical field stimulation-induced acetylcholine release from the same tissue preparations as those in these previous studies.…”

Section: Discussionsupporting

confidence: 84%

“…4(3-Phorbol-12,13-dibutyrate (PDBu) or 12-O-tetra decanoyl phorbol-13-acetate (TPA), an activator of pro tein kinase C, increased acetylcholine release induced by electrical stimulation from rabbit hippocampus in vitro (9) and the release induced by electrical stimulation or a high K+ concentration from the slices of the caudate nucleus of guinea pigs (10). A synaptosome preparation is known to contain high levels of protein kinase C (11) and its substrate proteins (12).…”

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confidence: 99%

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Muscarinic Autoinhibition and Modulatory Role of Protein Kinase C in Acetylcholine Release from the Myenteric Plexus of Guinea Pig Ileum.

Saitoh¹,

Fujimoto²,

Ishii

et al. 1997

Jpn.J.Pharmacol

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ABSTRACT-The modulatory role of protein kinase C on phospholipase A2, activation of which had been suggested to result in acetylcholine release from cholinergic neurons, was studied in longitudinal muscle preparations with the myenteric plexus of guinea pig ileum. The relationship of muscarinic autoinhibition to the modulation was also examined. Phorbol-12,13-dibutyrate (PDBu), an activator of protein kinase C, dose-dependently increased spontaneous and electrical field stimulation-induced acetylcholine releases from the preparation. The inhibitors of protein kinase C, staurosporine and calphostin C, inhibited the stimu latory effects of PDBu, but neither inhibitor affected spontaneous or electrical field stimulation-induced acetylcholine release in the absence of PDBu. On the other hand, atropine significantly increased electrical field stimulation-induced release by blocking a muscarinic autoinhibitory mechanism. Under the auto inhibition blocked condition, U73122, an inhibitor of phospholipase C, and staurosporine significantly inhibited the effect of atropine on electrical field stimulation-induced release. An inhibitor of phospholipase A2, mepacrine, inhibited PDBu-induced acetylcholine release and also inhibited the effect of atropine on electrical field stimulation-induced release. An activator of phospholipase A2, melittin, and a product of the phospholipase, arachidonic acid, increased the spontaneous and electrical field stimulation-induced releases. These results suggest that the phospholipase C protein kinase C system modulates acetylcholine release from cholinergic neurons by activating phospholipase A2 in the myenteric plexus of guinea pig ileum, and the activation of muscarinic autoreceptor may negatively modulate acetylcholine release at a point upstream of the system.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

Muscarinic Autoinhibition and Modulatory Role of Protein Kinase C in Acetylcholine Release from the Myenteric Plexus of Guinea Pig Ileum.

Saitoh¹,

Fujimoto²,

Ishii

et al. 1997

Jpn.J.Pharmacol

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“…One pathway that potentiates presynaptic secretion acts through protein kinase C (PKC, see Tanaka, 1984;Nichols et al,, 1987;Shu and Selmanoff, 1988;Shuntoh et al, 1988; see also Fig. 3).…”

Section: The Impact Of Presynaptic Receptor Activation On the Stimulumentioning

confidence: 99%

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

Verhage

Ghijsen

Silva

1994

Progress in Neurobiology

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“…Takuma and Ichida (32) reported that the combination of A23187 (I /_M) and phorbol 12-myristate 13-acetate (1 ,uM) induced a weak synergistic effect on amylase re lease (about 5%). This synergistic effect is much small er than that seen in other cell types (27)(28)(29)(30)(31). Our pre vious report (33) showed that an increase in DAG accumulation was involved in the potentiating effect of A23187 on carbachol-stimulated amylase release in parotid acinar cells and that this effect was additive.…”

Section: Analysis Of [3h]choline Metabolites Released Into the Mediummentioning

confidence: 69%

Ca2+ Ionophore and Phorbol Ester Stimulate Diacylglycerol Formation and Phosphatidylcholine Hydrolysis in Rat Parotid Acinar Cells

Komabayashi¹,

Yakata²,

Izawa³

et al. 1992

Japanese Journal of Pharmacology

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ABSTRACT-We investigated the effects of A23187 and phorbol 12,13-dibutyrate (PDBu) on sn-1,2 diacylglycerol (DAG) accumulation and phosphatidylcholine (PC) hydrolysis in rat parotid acinar cells. Both A23187 and PDBu, in concentration ranges of 0.001-0.1 uM, stimulated DAG accumulation and PC hydrolysis in a time and concentration-dependent manner. Treatment with A23187 and PDBu stimulated the release of [3H]choline and [3H]phosphocholine into the medium, indicating [3H]PC hy drolysis is due to the activation of phospholipases C and D; however, [3H]phosphatidylethanolamine hydrolysis was not indicated. These releases were unaffected by the addition of glucose 6-phosphate, a phosphatase inhibitor. Staurosporine, a protein kinase C inhibitor, significantly inhibited the DAG accumulation and the PC hydrolysis stimulated by these agents. Combinations of A23187 and PDBu potentiated the stimulatory effect which each of these agents alone had on DAG accumulation and PC hydrolysis. This mode of action was additive but not synergistic. These results suggest that DAG accu mulation induced by A23187 and PDBu is related to the PC hydrolysis mediated via the activation of phospholipases C and D, and that it is not related to phosphatidylethanolamine hydrolysis. Keywords:Parotid acinar cells, A23187, Phorbol 12,13-dibutyrate, sn-1,2-Diacylglycerol accumulation, Phosphatidylcholine hydrolysisAgonist binding to its receptor leads to phosphatidyl inositol 4,5-bisphosphate breakdown into sn-1,2-diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (1,4,5 IP3) via activation of inositol phospholipid-specific phospholipase C coupled with a GTP binding protein; DAG activates protein kinase C and 1,4,5-IP3 mobilizes Ca 2+ from the endoplasmic reticulum (1-4). These events are thought to play an important role in stimulus-secretion coupling (5 7).DAG was shown to be derived from phosphoino sitides, phosphatidylcholine (PC), and other lipids (7 10), but the relationship between DAG generation and their source during agonist stimulation is not fully understood. This may be due to the complexity of the kinetics of DAG formation; e.g., the kinetics of DAG formation varies with the agonist and the cell type. Re cently, PC hydrolysis has gained much attention, be cause DAG generated by protein kinase C-dependent PC-specific phospholipase C can provide a sustained activation of protein kinase C (11). In many cell types, CA 2+ ionophore or phorbol ester stimulates PC hy drolysis through phospholipase C and/or D and results in DAG accumulation. However, the mode (phospho lipase C, phospholipase D) by which these agents elicit DAG formation from PC varies with the cell type (12). As reviewed by Billah and Anthes (12), there are many reports concerning PC hydrolysis induced by Ca 2+ ionophore and phorbol esters, but the mechanism of PC hydrolysis in this system remains unknown.We therefore examined the effects of A23187 and phorbol 12,13-dibutyrate (PDBu) on DAG accumula tion and PC hydrolysis in rat parotid acinar cells. These results provide ...

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A phorbol ester and A23187 act synergistically to release acetylcholine from the guinea pig ileum

Cited by 76 publications

References 27 publications

Muscarinic Autoinhibition and Modulatory Role of Protein Kinase C in Acetylcholine Release from the Myenteric Plexus of Guinea Pig Ileum.

Muscarinic Autoinhibition and Modulatory Role of Protein Kinase C in Acetylcholine Release from the Myenteric Plexus of Guinea Pig Ileum.

Presynaptic plasticity: The regulation of Ca2+-dependent transmitter release

Ca2+ Ionophore and Phorbol Ester Stimulate Diacylglycerol Formation and Phosphatidylcholine Hydrolysis in Rat Parotid Acinar Cells

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