Use of [³H]-clozapine as a ligand of the dopamine D₄ receptor subtype in peripheral tissues

Authors: Ricci, A.¹; Bronzetti, E.²; Rossodivita, I.²; Amenta, F.¹

Source: Journal of Autonomic Pharmacology, Volume 17, Number 4, August 1997 , pp. 261-267(7)

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Abstract:

1 Molecular biology studies have documented the presence of peripheral dopamine D₄ receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands.

2 The atypical neuroleptic clozapine labelled with tritium ([³H]-clozapine) has been proposed and sold as a radioligand for brain dopamine D₄ receptors. However, the selectivity of [³H]-clozapine for D₄ receptor subtypes, and its specificity for brain dopamine receptors, have been questioned.

3 In this study dopamine D₄ receptors were assayed in peripheral organs known to express them, such as rat atria and kidney, by using a radioligand binding assay technique with [³H]-clozapine as the radioligand. Parallel experiments were performed using Chinese hamster ovary (CHO) cells transfected with the D₄ receptor clone (variant D_4.2).

4 [³H]-Clozapine was bound to sections of rat atria and kidney. After appropriate blockade of sites other than dopamine receptors to which it can bind (i.e. muscarinic cholinergic, serotonergic and α-adrenergic receptors), the radioligand was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D₄ receptor.

5 The above findings indicate that with appropriate protocols, [³H]-clozapine may represent a radioligand for peripheral dopamine D₄ receptors.

Document Type: Original article

DOI: http://dx.doi.org/10.1046/j.1365-2680.1997.00462.x

Affiliations: 1: Sezione di Anatomia Umana, Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Camerino, Italy, 2: Dipartimento di Scienze Cardiovascolari e Respiratorie, Università“La Sapienza”, Roma, Italy.

Publication date: 1997-08-01