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Regional Heterogeneity of Polyamine Effects on the N ‐Methyl‐D‐Aspartate Receptor in Rat Brain
Author(s) -
Subramaniam Swaminathan,
McGonigle Paul
Publication year - 1993
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.1471-4159.1993.tb03514.x
Subject(s) - spermidine , polyamine , spermine , nmda receptor , receptor , striatum , glutamate receptor , biochemistry , chemistry , agonist , dizocilpine , non competitive inhibition , biology , pharmacology , endocrinology , dopamine , enzyme
Polyamines have pronounced effects on N ‐methyl‐D‐aspartate (NMDA) receptors in vitro and may be important modulators of NMDA receptor activity in vivo. There is considerable regional heterogeneity in the effects of polyamines on [ 3 H]MK‐801 binding in rat brain sections. For example, spermidine enhances the binding of [ 3 H]MK‐801 to a much greater extent in the striatum than in the cortex. To further explore the basis for this regional heterogeneity, the effects of polyamines on [ 3 H]MK‐801 binding were measured in well‐washed membranes prepared from frontal cortex and striatum. There was no difference in the concentration‐response relationship for spermidine or the K D for [ 3 H]MK‐801 in the presence of 75 μ M spermidine, suggesting that the regional difference seen in tissue sections is due to an endogenous factor that is either removed or inactivated during the preparation of membranes. Comparison of spermidine concentration‐response curves in washed and unwashed tissue sections revealed that washing selectively enhanced the E max value in the ventromedial caudate putamen without changing the EC 50 . This is consistent with the possibility that a noncompetitive polyamine antagonist is being removed from this region during washing. There was no regional variability in the effects of the putative inverse agonist 1, 10‐diaminodecane, consistent with recent suggestions that this polyamine inhibits the NMDA receptor at a site distinct from the one at which polyamines act to enhance NMDA receptor function. Agents that modulate the redox state of the NMDA receptor did not eliminate the regional heterogeneity of polyamine effects. Furthermore, the stimulatory effect of glycine in these regions did not correlate with that of spermidine. These results suggest the existence of one or more endogenous factors that noncompetitively influence the effects of polyamines in a regionspecific manner.