Biphasic effects of magnesium on the [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine binding in the rat cerebral cortex.

Mg2+ at micromolar concentrations greatly enhanced [3H]N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([3H]TCP) binding to well-washed rat cortical membranes, whereas [3H]TCP binding was inhibited by Mg2+ at concentrations higher than 1 mM. In the presence of either L-glutamate (10 microM) or glycine (10 microM), 30 microM Mg2+ caused further stimulation of [3H]TCP binding, suggesting that a high-affinity site for Mg2+ is distinct from the glutamate or glycine binding site. These findings indicate that Mg2+ acts on at least two different recognition sites, e.g. a novel high-affinity site for Mg2+ which stimulates [3H]TCP binding and the Mg2+ recognition site located within the ion channel.