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.
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.
INSERM U. 254, Hôpital Saint Charles, Montpellier, France.
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Guiramand
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Vignes
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Récasens
D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002413:Cations, Divalent; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007295:Inositol Phosphates / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D016548:Prosencephalon / Q000378:metabolism*; D016318:Quisqualic Acid / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002413:Cations, Divalent; D005971:Glutamates; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D018091:Receptors, AMPA; D017981:Receptors, Neurotransmitter; D002104:Cadmium; D000001:Calcimycin; D018698:Glutamic Acid; D016318:Quisqualic Acid; D002217:Carbachol; D011188:Potassium; D002118:Calcium