[3H]-quinelorane binds to D2 and D3 dopamine receptors in the rat brain

SL Gackenheimer, JM Schaus and DR Gehlert

Lilly Research Laboratories, A Division of Eli Lilly and Company, Indianapolis, Indiana, USA.

Quinelorane is a BCD partial ergoline with potent dopaminergic effects in vitro and in vivo. Partial ergoline compounds of this series consist of the B-, C- and D-rings of the four ring ergoline skeleton. Many of the pharmacological effects of quinelorane are believed to be due to stimulation of the D2 subtype of the dopamine receptor. Recently, a D3 dopamine receptor was identified that is insensitive to guanine nucleotides and exhibits an unusual distribution in the brain. When this receptor is expressed in Chinese hamster ovary cells, quinelorane has higher affinity for the D3 receptor than the D2 receptor. To further define the pharmacology of quinelorane, we have synthesized [3H]-quinelorane and examined its binding to sections of rat brain in vitro. [3H]-quinelorane bound with high affinity (KD = 1.8 nM) and exhibited very low nonspecific binding. D2 selective antagonists, such as (+)butaclamol and spiperone, were potent inhibitors of binding while the D1 antagonist SCH23390 was significantly less potent. A majority of the binding was inhibited in a concentration-dependent manner by guanylyl-imidodiphosphate with a maximal inhibition at concentrations of 1 microM and greater. Autoradiographic studies were performed in the presence and absence of 10 microM Gpp(NH)p. Binding in D2 containing regions, such as the caudate-putamen, was completely inhibited by guanylyl-imidodiphosphate although binding in D3 containing areas, such as the islands of Calleja, was unaffected. Therefore, [3H]-quinelorane is an excellent agonist radioligand for the localization of D2 and D3 receptors in rat brain.

Volume 274, Issue 3, pp. 1558-1565, 09/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics

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