Pharmacological characterization and autoradiographic localization of a putative dopamine D₄ receptor in the heart

Authors: Ricci A.; Bronzetti E.; Fedele F.; Ferrante F.; Zaccheo D.; Amenta F.

Source: Journal of Autonomic Pharmacology, Volume 18, Number 2, April 1998 , pp. 115-122(8)

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Abstract:

1 The pharmacological profile and the anatomical localization of a putative dopamine D₄ receptor were assessed in sections of rat and human atria and ventricles using combined radioligand binding and autoradiographic techniques with [³H]-spiperone as a ligand.

2 [³H]-Spiperone was bound specifically to sections of human and rat atria and ventricles. The binding was time-, temperature- and concentration-dependent, belonging to a single class of high-affinity sites. In atria, the dissociation constant value (K_d) was 0.45 nm in rats and 0.32 nm in humans, and the maximum density of binding sites (B_max) was 31.6 ± 2.9 fmol mg^--1 tissue in rats and 18.8 ± 0.7 fmol mg^--1 tissue in humans. In ventricles, K_d was 0.38 nm in rats and 0.39 nm in humans, and the B_max was 43.5 ± 3.0 fmol mg^--1 tissue in rats and 56.4 ± 3.2 fmol mg^--1 tissue in humans.

3 The pharmacological profile of [³H]-spiperone binding to sections of both rat and human atria and ventricles was consistent with the labelling of dopamine D₂-like receptors. [³H]-Spiperone binding was more sensitive to displacement by the neuroleptic clozapine in sections of atria than of ventricles, suggesting the expression of a dopamine D₄ receptor in atrial tissue. Moreover, pre-incubation of some sections with a dopamine D₄ receptor antibody and subsequent exposure to [³H]-spiperone caused a remarkable decrease of radioligand binding to sections of atria, but only a slight reduction of binding to sections of ventricles.

4 Light microscope autoradiography revealed the accumulation of silver grains over atrial tissue within atrial myocardiocytes. A higher density of silver grains was developed in rat than in human atria. In ventricles, silver grains were accumulated primarily in cluster areas both in rats and in humans.

5 The above findings suggest the expression of a dopamine D₄ receptor in rat atria, but not in ventricles. A similar site was identified in human atria. The possible relevance of a dopamine D₄ receptor in the heart is discussed.

Language: English

Document Type: Research article

Publication date: 1998-04-01