Abstract
We have examined the ability of divalent and trivalent cations to regulate [3H]MK801 binding to the N-methyl-D- aspartate operated ionophore of rat brain membranes. In EDTA-washed membranes that are nominally free of glutamate and glycine the cations Ba2+, Ca2+, Co2+, La3+, Mn2+,and Sr2+ increased [3H]MK801 binding in the range 0.01-10 mM, depending on the cation studied. At higher concentrations (0.1-30 mM) these cations all inhibited binding. In contrast, Cd2+, Hg2+, Mg2+, Ni2+ and Zn2+ inhibited binding at all concentrations tested. The addition of maximally effective concentrations of glutamate (100 μM) and glycine (30 μM) increased binding by some 200% above control. In the presence of glutamate and glycine all cations except Sr2+ only inhibited binding, while the stimulation produced by Sr2+ was markedly diminished. The potency of most of the divalent cations tested was increased in the presence of glutamate and glycine. In contrast, Cd2+ and Zn2+ became less potent, while the potency of Hg2+ did not change. Thus, it appears that cations regulate the function of the N-methyl-D-aspartate receptor/ ionophore complex by interacting with at least two separate sites.
Original language | English (US) |
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Pages (from-to) | 103-112 |
Number of pages | 10 |
Journal | European Journal of Pharmacology |
Volume | 151 |
Issue number | 1 |
DOIs | |
State | Published - Jun 22 1988 |
Funding
ported by Public Health Service Grants DA02121, DA 02575, MH 40165, grants from Miles and Marion Pharmaceuticals to R.J.M., and by a grant from the Scottish Rite Schizophrenia Research Program NMJ (U.S.A.) to I.J.R. and R.J.M.
Keywords
- Ca
- Excitatory amino acid
- Glutamate receptors
- Glycine
- MK801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate)
- Mg
- Zn
ASJC Scopus subject areas
- Pharmacology