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Biochemical Responses Mediated by N ‐Methyl‐ d ‐Aspartate Receptors in Rat Cortical Slices Are Differentially Sensitive to Magnesium
Author(s) -
Gonzales Rueben A.
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb09758.x
Subject(s) - nmda receptor , carbachol , magnesium , chemistry , stimulation , inhibitory postsynaptic potential , endocrinology , medicine , receptor , biochemistry , biology , organic chemistry
The effects of magnesium on the inhibition of phosphoinositide (PI) hydrolysis and the stimulation of [ 3 H]norepinephrine release by N ‐methyl‐ d ‐aspartate (NMDA) in rat cortical slices were investigated. Removal of the magnesium from the buffer resulted in a small reduction of the inhibitory effect of 100 μ M NMDA (34% inhibition in the absence of magnesium, compared with 51% for the control) when slices were coincubated with NMDA and carbachol. Addition of 10 m M Mg 2+ also allowed the inhibitory effect of 100 μ M NMDA on carbachol‐stimulated PI hydrolysis to be expressed (44% inhibition) under these conditions. Concentration–effect curve analysis for the NMDA‐induced inhibition of carbachol‐stimulated PI hydrolysis indicated that the IC 50 for NMDA was decreased from 14.9 μ M for the control to 4.2 μ M in the absence of magnesium. The absence of magnesium also had small effects on the concentration–effect curve for (+)‐5‐methyl‐10,11‐dihydro‐5 H ‐dibenzo[ a,d ]cyclohepten‐5,10‐imine hydrogen maleate reversal of the inhibitory effects of NMDA on carbachol‐stimulated PI hydrolysis. The absence of magnesium also shifted slightly downward and flattened the NMDA concentration–effect curve if the cortical slices were pretreated with NMDA in the presence or absence of magnesium followed by removal of the NMDA and subsequent stimulation with carbachol. In contrast, cortical slices that had been prepared and treated similarly to the slices used in the PI experiments were very sensitive to the inhibitory effects of magnesium when using the NMDA stimulation of [ 3 H]norepinephrine release assay in the presence or absence of carbachol. Thus, the modulation of PI hydrolysis by NMDA is much less sensitive to inhibition by magnesium than is the stimulation of neurotransmitter release. It is possible that NMDA receptors that mediate the inhibition of PI hydrolysis are coupled to ion channels that do not possess the characteristic voltage‐dependent blockade by Mg 2+ .