Pituitary and brain D2 receptor density measured in vitro and in vivo in EEDQ treated male rats.
The effect of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) (20 mg/kg, 24 h) on dopamine D2 receptor density in rat pituitary and brain was measured using in vitro and in vivo radioligand binding techniques. In the in vitro radioligand binding experiments EEDQ was found to reduce the density (Bmax) of [3H]-spiperone binding sites in the striatum by 86% while in the pituitary the corresponding decrease was only 37%. The affinity (KD) of the remaining striatal and pituitary D2 receptors was not different in EEDQ treated animals as compared to controls. When D2 receptor density was measured in vivo the effect of EEDQ was less pronounced. Thus, in rats given EEDQ the specific binding of either of the two D2 ligands [3H]-raclopride or [3H]-spiperone (administered in a single dose) in striatum and in the limbic forebrain was reduced by 45-62%; moreover, no significant decrease in pituitary D2 receptor density was observed. The data are discussed in relation to the finding (presented in a separate paper) that the same dose of EEDQ that failed to influence pituitary D2 receptor density as measured in vivo effectively antagonizes the prolactin decreasing effect of the partial D2 agonist (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine [(-)-3-PPP].
Ekman
A
A
Department of Pharmacology, University of Göteborg, Sweden.
Eriksson
E
E
D015107:4-Butyrolactone / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D007700:Kinetics; D008032:Limbic System / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism*; D011804:Quinolines / Q000494:pharmacology*; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D012457:Salicylamides / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D014316:Tritium
D011804:Quinolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D014316:Tritium; D020891:Raclopride; D013134:Spiperone; C000470:EEDQ; D015107:4-Butyrolactone