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Polyamines Modulate the Binding of [ 3 H]MK‐801 to the Solubilized N ‐Methyl‐D‐Aspartate Receptor
Author(s) -
Romano Carmelo,
Williams Keith,
Molinoff Perry B.
Publication year - 1991
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.1471-4159.1991.tb08223.x
Subject(s) - spermidine , spermine , nmda receptor , receptor , polyamine , dizocilpine , biochemistry , chemistry , ifenprodil , binding site , glutamate receptor , stereochemistry , membrane , enzyme
Spermine and spermidine enhance the binding of [ 3 H](+)‐5‐methyl‐10,11‐dihydro‐5 H ‐dibenzo[ a, d ]cyclohepten‐5,10‐imine ([ 3 H]MK‐801) to N ‐methyl‐D‐aspartate (NMDA) receptors in membranes prepared from rat brain. These polyamines also enhance binding of [ 3 H]MK‐801 to NMDA receptors that have been solubilized with deoxycholate. Other polyamines selectively antagonize this effect, a finding indicating that the polyamine recognition site retains pharmacological and structural specificity after solubilization. In the presence of spermidine, an increase in the affinity of the solubilized NMDA receptor for [ 3 H]MK‐801 is observed. However, the rates of both association and dissociation of [ 3 H]MK‐801 binding to solubilized NMDA receptors are accelerated when assays are carried out in the presence of spermidine. When kinetic data are transformed, pseudo‐first‐order association and first‐order dissociation plots are nonlinear in the presence of spermidine, an observation indicating a complex binding mechanism. Effects of spermidine on solubilized NMDA receptors are similar to effects previously described in studies of membrane‐bound receptors. The data indicate that polyamines interact with a specific recognition site that remains associated with other components of the NMDA receptor complex after detergent solubilization.