Differential recovery rates of rat D2 dopamine receptors as a function of aging and chronic reserpine treatment following irreversible modification: a key to receptor regulatory mechanisms.
The density of D2 dopamine receptors identified by 3H-spiperone binding was significantly lower in the striatum of senescent (28-month-old) than in mature (4-month-old) Fischer 344 rats. The time course of recovery of 3H-spiperone binding to D2 dopamine receptors following irreversible receptor modification by a single injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was significantly slower in senescent than in mature rats. The kinetics of D2 dopamine receptor repopulation could be adequately described by a model assuming a constant rate of receptor production and a rate of degradation that was dependent on receptor concentration. Both the production rate and degradation rate constant of D2 dopamine receptors were lower in the senescent rats compared to mature rats. The changes in receptor density that occur as a function of development and aging are the result of changes in both the receptor production rate and receptor degradation rate constant, which, while both are reduced, tend to maintain receptor density. That is, receptor density decreased by 26% from 4 to 28 months of age, although the receptor production rate and degradation rate constant decreased by 40-50%. Chronic treatment of rats with reserpine produced a 21% increase in the density of striatal D2 dopamine receptors of mature, but not senescent, rats, accompanied by an increase in the initial recovery rate of 3H-spiperone binding sites following EEDQ treatment. It might have been expected that the reduced formation of agonist-bound receptors would have lead to a decrease in the receptor degradation rate constant.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012110:Reserpine / Q000494:pharmacology*; D013134:Spiperone
D011804:Quinolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D006165:Guanylyl Imidodiphosphate; D013134:Spiperone; C009074:N-n-propylnorapomorphine; C000470:EEDQ; D012110:Reserpine; D006220:Haloperidol; D001058:Apomorphine