D-2 dopamine receptors in aging mouse striatum: determination of high- and low-affinity agonist binding sites.
Striatal D-2 dopamine receptors in homogenates from aged male C57BL/6J mice were examined for high and low-affinity agonist binding. High-affinity dopamine binding requires the ternary complex of the D-2 receptor and a guanine nucleotide binding regulatory protein (N). Thus, changes in the interaction of D-2 and N could contribute to previously reported changes in agonist binding in aged rodents and humans. Qualitative experiments indicated no age-change in the ability of guanine nucleotides to reduce the apparent potency of dopamine at D-2 receptors. Also, no age differences were observed in the ability of guanine nucleotides to decrease N-[3H]propylnorapomorphine binding, suggesting that the ability of guanine nucleotides to dissociate D-2 and N was similar with age. Quantitative determination of the high- (RH) and low-affinity (RL) agonist binding components of striatal D-2 dopamine receptors in the absence of guanine nucleotides indicated differences in the density of RH, and the percentage of D-2 receptors measured as RH, between the ages of 3 and 12 months. No changes in RH or percentage of RH occurred after midlife. In contrast, the total D-2 receptor population, [3H]spiperone maximum binding, declined progressively from 3 to 24 months. Age-changes were restricted to D-2 receptor density; the dissociation constants for agonist and antagonist binding were similar across age. The data suggest that age-changes in striatal D-2 dopamine receptors can occur in the density of the D-2 receptor and in the mechanism that confers the property of high-affinity agonist binding upon the D-2 receptor.
Severson
J A
JA
Randall
P K
PK
D000375:Aging; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D019204:GTP-Binding Proteins; D004298:Dopamine