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

Abstract

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.

Glutamate Regulates the Frequency of Spontaneous Synchronized Ca2+ Spikes Through Group II Metabotropic Glutamate Receptor in Cultured Mouse Cortical Networks

“…Glial cells expressing mGluRs might be activated by glutamate released by neurons, and then indirectly regulate the frequency of neural Ca 2+ spikes. Some reports have indicated that glutamate acting on mGluRs increases intracellular Ca 2+ concentrations in astrocytes (Guiramand et al, 1991;Jensen and Chiu, 1990) in addition to neurons (Courtney et al, 1990;Llano et al, 1991). However, changes in the frequency of synchronized Ca 2+ spikes according to the activation of the mGluRs in this report were changes of neural Ca 2+ spikes, because they were accompanied by action potentials, and small cell bodies of neurons visualized by fura-2 apparently differed from the flat, practically invisible in the present experiments, morphology of astrocytes (Suzuki et al, 2003).…”

α‐1 adrenergic input to solitary nucleus neurones: calcium oscillations, excitation and gastric reflex control

“…Specifically, the bathing solution was switched to either zero calcium–EGTA Krebs solution or the Ca 2+ was replaced by Cd 2+ . Predictably (Ciardo & Meldolesi, 1991; Guiramand et al 1991), both of these conditions essentially blocked the effects of glutamate to elevate cytoplasmic Ca 2+ in NST neurones (data not shown).…”

A Specific Trarisduction Mechanism for the Glutamate Action on Phosphoinositide Metabolism via the Quisqualate Metabotropic Receptor in Rat Brain Synaptoneurosomes: I. External Na+ Requirement

“…In addition, we have shown that some divalent cations, such as Cd2+ and Ba2+, stimulate formation of IPS and depolarize the synaptoneurosomal membrane (see Guiramand et al, 1991). The stimulation of formation of Ips by Cd" has also been reported in human skin fibroblasts (Smith et al, 1989).…”