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 Ca 2+ 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 Ca 2+ 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 Ca 2+ concentration in synaptoneurosome preparations as measured by the fura‐2 assay. The absence of external Ca 2+ decreases basal and Glu‐, and K + ‐stimulated formation of IPs. Cd 2+ (100 μ M ) fully inhibits both Gluand K + ‐evoked formation of IPs without affecting the carbachol‐elicited response of IPs. Zn 2+ inhibits Gluand K + ‐stimulated accumulation of IPs (IC 50 ∽ 0.4 m M ) but with a lower affinity than Cd 2+ (IC 50 ∽ 0.035 m M ). The organic Ca 2+ channel blockers verapamil (10 μ M ), nifedipine (10 μ M ), ω‐conotoxin (2 μ M ), and amiloride (10 μ M ) as well as the inorganic blockers Co 2+ (100 μ M ) and La 3+ (100 μ M ) block neither Glunor K + ‐evoked formation of IPs, a result suggesting that the opening of the L‐, T‐, N‐, or P‐type Ca 2+ channels does not participate in these responses. All these data suggest that an increase in intracellular Ca 2+ concentration resulting from an influx of Ca 2+ , sensitive to Cd 2+ but not to other classical Ca 2+ antagonists, may play a key rote in the transduction mechanism activated by Glu or depolarizing agents.