Differential serotonin2 receptor recovery in mature and senescent rat brain after irreversible receptor modification: effect of chronic reserpine treatment.
We report here the differential time course of recovery of [3H]ketanserin-labeled serotonin2 (5-HT2) receptors in frontal cortex of mature (4 months old) and senescent (28 months old) male Fischer 344 rats. We provide evidence that the irreversible modification of 5-HT2 serotonin receptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline occurs at the ligand binding site and that this treatment does not appear to affect the interaction of these receptors with their guanine nucleotide regulatory protein. Senescent rats exhibited significantly reduced (-20%) maximum receptor density levels of 5-HT2 receptors compared with their mature counterparts. The time course of recovery of [3H] ketanserin binding to 5-HT2 receptors after irreversible receptor modification by a single peripheral injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline was significantly slower in senescent rats. The slower recovery was a function of decreases in both the receptor production rate and the degradation rate constant in senescent rats compared with mature rats. Interestingly, chronic reserpine treatment resulted in a significant decrease in control maximum receptor density values in both mature (-17%) and senescent (-18%) rats. Although the receptor production rate and receptor degradation rate constants in both mature and senescent reserpinized rats were slightly decreased, there was no significant change in the overall rates of receptor recovery when compared with their respective age-matched nonreserpinized counterparts. These data indicate that both the steady state levels and "turnover" of 5-HT2 receptors are decreased in senescence and that these receptors can be down-regulated by chronic reserpine treatment.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D011804:Quinolines; D011985:Receptors, Serotonin; D006165:Guanylyl Imidodiphosphate; C000470:EEDQ; D012110:Reserpine; D007650:Ketanserin; D019204:GTP-Binding Proteins