Denervation accelerates the reappearance of neostriatal D-2 receptors after irreversible receptor blockade.
The effect of denervation on the turnover of striatal dopaminergic D-2 receptors was examined by determining the rate of receptor reappearance in vivo after administration of the irreversible receptor antagonist, N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats that received prior unilateral intracerebral injection of 6-hydroxydopamine (6-OHDA). Initial experiments confirmed that EEDQ (10 mg/kg i.p.) induces a severe, prolonged blockade of D-2 receptors. Recovery of [3H]spiroperidol binding occurred at a rate of approximately 9% of control binding per day. 6-OHDA injection into the ascending dopaminergic projection 3 or 5 days prior to EEDQ administration revealed that denervation had no effect on the rate of D-2 receptor recovery during the first post-operative week. By 4-5 weeks postoperatively, however, denervation enhanced the rate of recovery of [3H]spiroperidol binding. These results are consistent with our finding that, when homogenized tissue preparations are used, steady-state receptor density does not change within the first postoperative week but increases by 3-4 weeks after the injury. Saturation analysis determined that both EEDQ and denervation altered the density of binding sites, whereas neither treatment significantly affected the affinity of the receptor for [3H]spiroperidol. By 4-5 weeks postoperatively, the receptor degradation rate constant in the denervated striatum (0.0054/h) was equal to that in the intact striatum (0.0052/h). Thus, only the receptor reappearance rate was elevated in the denervated striatum (3.8 fmol/mg protein/h) relative to the intact striatum (2.8 fmol/mg protein/h).
Neve
K A
KA
Loeschen
S
S
Marshall
J F
JF
D000818:Animals; D003342:Corpus Striatum / Q000032:analysis* / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D016627:Oxidopamine; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000032:analysis*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D006892:Hydroxydopamines; D011804:Quinolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; C000470:EEDQ; D016627:Oxidopamine; D004298:Dopamine