Is Inositol Bisphosphate the Product of A23187 and Carbachol‐Mediated Polyphosphoinositide Breakdown in Synaptosomes?

Brammer, Michael; Hajimohammadreza, Iradj; Sardiwal, Sudesh; Weaver, Keith

doi:10.1111/j.1471-4159.1988.tb01068.x

Cited by 33 publications

(14 citation statements)

References 18 publications

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“…(b) A23 187, a Ca2+ ionophore, activates formation of IPS (Fig. 4), in agreement with previous reports (Griffin and Hawthorne, 1978;Kendall and Nahorski, 1984;Brammer et al, 1988;Brammer and Weaver, 1989). (c) The A23 187-induced accumulation of IPS is not additive with that evoked by Glu or K+ (Fig.…”

Section: The Putative Common Step In the Action Of Glu And Depolarizisupporting

confidence: 92%

A Specific Transduction Mechanism for the Glutamate Action on Phosphoinositide Metabolism via the Quisqualate Metabotropic Receptor in Rat Brain Synaptoneurosomes: II. Calcium Dependency, Cadmium Inhibition

Guiramand¹,

Vignes²,

Récasens³

1991

Journal of Neurochemistry

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In this article, we demonstrate that an increase in intracellular Ca2+ concentration may represent a specific common step(s) in the mechanism(s) of action of glutamate (Glu) and depolarizing agents on formation of inositol phosphates (IPs) in 8-day-old rat forebrain synaptoneurosomes. In fact, A23187, a Ca2+ ionophore, induces a dose-dependent accumulation of IPs, which is not additive with that evoked by Glu and K+ but is slightly synergistic with that induced by carbachol. In addition, Glu and K+ augment the intracellular Ca2+ concentration in synaptoneurosome preparations as measured by the fura-2 assay. The absence of external Ca2+ decreases basal and Glu-, and K(+)-stimulated formation of IPs. Cd2+ (100 microM) fully inhibits both Glu- and K(+)-evoked formation of IPs without affecting the carbachol-elicited response of IPs. Zn2+ inhibits Glu- and K(+)-stimulated accumulation of IPs (IC50 approximately 0.4 mM) but with a lower affinity than Cd2+ (IC50 approximately 0.035 mM). The organic Ca2+ channel blockers verapamil (10 microM), nifedipine (10 microM), omega-conotoxin (2 microM), and amiloride (10 microM) as well as the inorganic blockers Co2+ (100 microM) and La3+ (100 microM) block neither Glu- nor K(+)-evoked formation of IPs, a result suggesting that the opening of the L-, T-, N-, or P-type Ca2+ channels does not participate in these responses. All these data suggest that an increase in intracellular Ca2+ concentration resulting from an influx of Ca2+, sensitive to Cd2+ but not to other classical Ca2+ antagonists, may play a key role in the transduction mechanism activated by Glu or depolarizing agents.

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Section: The Putative Common Step In the Action Of Glu And Depolarizisupporting

confidence: 92%

A Specific Transduction Mechanism for the Glutamate Action on Phosphoinositide Metabolism via the Quisqualate Metabotropic Receptor in Rat Brain Synaptoneurosomes: II. Calcium Dependency, Cadmium Inhibition

Guiramand¹,

Vignes²,

Récasens³

1991

Journal of Neurochemistry

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“…forming divalent selective cation ionophores that allow Ca2+ to enter the cytosol from both the extracellular space and from cellular storage sites (Pressman, 1976;Pozzan et al, 1994). Calcimycin may also raise [Ca2+], indirectly through stimulation of phosphoinositide hydrolysis (Fisher & Agranoff, 1981;Brammer et al, 1988;Brammer & Weaver, 1989), although it exhibits a pattern of inositol polyphosphate formation unlike that which results from activation of cell surface receptors that couple to PLC (Baird & Nahorski, 1990).…”

Section: Discussionmentioning

confidence: 99%

Action of 5‐hydroxytryptamine in facilitating N‐methyl‐D‐aspartate depolarization of cortical neurones mimicked by calcimycin, cyclopiazonic acid and thapsigargin

Rahman

Neuman

1996

British J Pharmacology

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1 The ability of calcimycin, cyclopiazonic acid and thapsigargin to facilitate the N-methyl-D-aspartate (NMDA)-mediated depolarization of cortical projection neurones was investigated by use of grease-gap recording and the results compared with the facilitation that results from activation of 5-hydroxytryptamine2A receptors.2 Calcimycin (0.25 to 3 gM), cyclopiazonic acid (5 to 30 gM), and thapsigargin (10 to 300 nM) reversibly facilitated the NMDA (50 gM)-induced depolarization in the presence of tetrodotoxin. The concentration-response relationships were bell-shaped with a mean enhancement of 550% for calcimycin(1 gM) and approximately 400% for cyclopiazonic acid (20 gM) and thapsigargin (100 nM). At the highest concentration of each agent tested, no facilitation was observed.3 Chlorpromazine (1 gM) partially restored a facilitation at 3 gM calcimycin and 300 nM thapsigargin.Myo-inositol (10 mM) and 100 nM staurosporine were both ineffective in this regard. 4 The depolarization elicited by 10 gM quisqualate or 5 gM kainate was not facilitated by 10 pM cyclopiazonic acid.5 Calcimycin (0.5 gM), cyclopiazonic acid (20 gM), and thapsigargin (100 nM) elicited a significant facilitation in the presence of an antagonist cocktail consisting of D,L-2-amino-3-phosphonopropionic acid, prazosin, ritanserin, and scopolamine, although the magnitude of the facilitation was reduced. 6 Facilitation of the NMDA depolarization elicited by both 30 gM 5-hydroxytryptamine and 10 pM phenylephrine was eliminated in nominally Mg2"-free medium. In contrast, the facilitation induced by 0.5 gM calcimycin remained intact.7 Bis-(o-aminophenoxy)-ethane-N,N,N,N, tetraacetic acid aminoethoxy (50 gM) or perfusion with nominally Ca2+-free medium eliminated facilitation of the NMDA depolarization induced by 30 gM 5-hydroxytryptamine and 100 nM thapsigargin. 8 The facilitation induced by both 30 gM 5-hydroxytryptamine and 1 guM calcimycin was reduced in a concentration-dependent manner by nifedipine (1 to 10 gM).9 Calcimycin, cyclopiazonic acid and thapsigargin facilitate the NMDA depolarization in a manner which closely mimics the facilitation induced by 5-hydroxytryptamine. It is concluded that enhancement of the NMDA depolarization at cortical projection neurones results from an elevation of Ca2+ in the cytosol and that several sources of Ca2+ contribute to the facilitation.

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“…Carbachol stimulates PPI breakdown in synaptosomes and synaptoneurosomes by acting on mAChR (Fisher and Agranoff, 198 1 ;Gusovsky et al, 1986;Audigier et al, 1988;Brammer et al, 1988). Inositol 1,4,5trisphosphate (IP3), a product of cleavage of phosphatidylinositol 4,5-bisphosphate by phospholipase C (PLC), and muscarine have been reported to release 45Ca2+ from synaptosomes made permeable with saponin (Gandhi and Ross, 1987), suggesting mobilisation of intracellular calcium as a consequence of muscarinic stimulation.…”

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confidence: 99%

Stimulation of Muscarinic Acetylcholine Receptors Increases Synaptosomal Free Calcium Concentration by Protein Kinase‐Dependent Opening of L‐Type Calcium Channels

Boess

Balasubramanian

Brammer

et al. 1990

Journal of Neurochemistry

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In synaptosomes prepared from rat cerebral cortex, free cytosolic calcium concentration ([Ca2+]i) was measured using the fluorescent dye fura-2. Incubation of fura-2-loaded synaptosomes with carbachol increased [Ca2+]i in a dose-dependent manner (1-1,000 microM), with a maximum response of 22 +/- 2% at approximately 100 microM and an EC50 (calculated concentration producing 50% of the maximum response) of 30 microM. The effect of carbachol (100 microM) on [Ca2+]i was antagonised by atropine, but not by hexamethonium (10 microM). The calculated concentration of atropine needed for 50% inhibition (IC50) was 260 nM. The rise in [Ca2+]i produced by carbachol was reduced in the absence of extrasynaptosomal Ca2+ and effectively blocked by the L-type calcium channel blocker nifedipine (with an IC50 of 29 nM). The response to carbachol was reduced if the synaptosomes were preincubated with the protein kinase inhibitors H7 [1-(5-isoquinolinylsulfonyl)-2- methylpiperazine] (from 17% in the solvent control to 4%) and staurosporine (from 20% in the solvent control to 3%). These results show that stimulation of muscarinic acetylcholine receptors in synaptosomes increases [Ca2+]i by protein kinase-dependent activation of 1,4-dihydropyridine-sensitive calcium channels.

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Is Inositol Bisphosphate the Product of A23187 and Carbachol‐Mediated Polyphosphoinositide Breakdown in Synaptosomes?

Cited by 33 publications

References 18 publications

A Specific Transduction Mechanism for the Glutamate Action on Phosphoinositide Metabolism via the Quisqualate Metabotropic Receptor in Rat Brain Synaptoneurosomes: II. Calcium Dependency, Cadmium Inhibition

A Specific Transduction Mechanism for the Glutamate Action on Phosphoinositide Metabolism via the Quisqualate Metabotropic Receptor in Rat Brain Synaptoneurosomes: II. Calcium Dependency, Cadmium Inhibition

Action of 5‐hydroxytryptamine in facilitating N‐methyl‐D‐aspartate depolarization of cortical neurones mimicked by calcimycin, cyclopiazonic acid and thapsigargin

Stimulation of Muscarinic Acetylcholine Receptors Increases Synaptosomal Free Calcium Concentration by Protein Kinase‐Dependent Opening of L‐Type Calcium Channels

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