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Titolo:
Modulation of [H-3]quinpirole binding at striatal D-2 dopamine receptors by a monoamine oxidase(A)-like site - Evidence from radioligand binding studies and D-2 receptor- and MAO(A)-deficient mice
Autore:
Levant, B; Morgan, KA; Ahlgren-Beckendorf, JA; Grandy, DK; Chen, K; Shih, JC; Seif, I;
Indirizzi:
Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA Univ Kansas Kansas City KS USA 66160 Therapeut, Kansas City, KS 66160 USA Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR USA Oregon Hlth Sci Univ Portland OR USA ysiol & Pharmacol, Portland, OR USA Univ So Calif, Sch Med, Dept Mol Pharmacol & Toxicol, Los Angeles, CA USA Univ So Calif Los Angeles CA USA harmacol & Toxicol, Los Angeles, CA USA Inst Curie, Unite Mixte Rech 146, CNRS, Orsay, France Inst Curie Orsay France urie, Unite Mixte Rech 146, CNRS, Orsay, France
Titolo Testata:
LIFE SCIENCES
fascicolo: 2, volume: 70, anno: 2001,
pagine: 229 - 241
SICI:
0024-3205(20011130)70:2<229:MO[BAS>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
H-3 QUINPIROLE BINDING; C57BL/6 MOUSE-BRAIN; OXIDASE INHIBITORS; RAT-BRAIN; SIGMA-LIGANDS; BEHAVIOR; SENSITIZATION; MEMBRANES; PROFILE; MODELS;
Keywords:
quinpirole; monoamine oxidase; monoamine oxidase inhibitor; striatum; rat;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
25
Recensione:
Indirizzi per estratti:
Indirizzo: Levant, B Univ Kansas, Med Ctr, Dept Pharmacol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA Univ Kansas 3901 Rainbow Blvd Kansas City KS USA 66160 66160 USA
Citazione:
B. Levant et al., "Modulation of [H-3]quinpirole binding at striatal D-2 dopamine receptors by a monoamine oxidase(A)-like site - Evidence from radioligand binding studies and D-2 receptor- and MAO(A)-deficient mice", LIFE SCI, 70(2), 2001, pp. 229-241

Abstract

[H-3]Quinpirole is a dopamine agonist with high affinity for the D-2 and D-3 dopamine receptors. A variety of monoamine oxidase inhibitors (MAOIs) inhibit equilibrium binding of [H-3]quinpirole binding in rat striatal membranes suggesting that MAOIs interact with a novel binding site that is labeled by [H-3]quinpirole or that allosterically modulates [H-3]quinpirole binding. To determine whether the D-2 receptor is essential for [H-3]quinpirole binding and/or modulation of [H-3]quinpirole binding by MAOIs, D-2 receptor-deficient mice were studied. [H-3]Quinpirole binding was decreased in D-2 receptor-deficient mice to 3% of that observed in wild-type controls indicating that [H-3]quinpirole binding is associated with the D-2 dopamine receptors. Then, in an attempt to label the site mediating the modulation of [H-3]quinpirole binding, binding of the MAOI [H-3]Ro 41-1049 was characterizedin rat striatal membranes. [H-3]Ro-41-1049 labeled a single binding site with a pharmacological profile with respect to MAOIs that was similar to both [H-3]quinpirole binding (Spearman r=0.976) and MAO(A) activity. To determine whether MAO(A) plays a role in the modulation of [H-3]quinpirole binding by MAOIs, MAO(A)- deficient mice were examined. In these mice, [H-3]Ro-41-1049 binding was decreased to 7% of wild-type control. [H-3]Spiperone binding was unaltered. Spiperone-displaceable [H-3]quinpirole binding was decreased to 43% of wild-type control; however, the remaining [H-3]quinpirole binding in MAO(A)- deficient animals was inhibited by Ro 41-1049 similar to wild-type. [H-3]Ro-41-1049 binding was not decreased in D-2 receptor-deficient mice. These data suggest that [H-3]Ro-41-1049 labels multiple sites and that MAOIs modulate [H-3]quinpirole binding to the D-2 receptor via interactions at a novel, non-MAO binding site with MAO(A)-like pharmacology. (C) 2001 Elsevier Science Inc. All rights reserved.

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Documento generato il 09/04/20 alle ore 20:08:16