PHARMACOLOGICAL CHARACTERIZATION AND AUTORADIOGRAPHIC LOCALIZATION OFA PUTATIVE DOPAMINE D-4 RECEPTOR IN THE HEART

1 The pharmacological profile and the anatomical localization of a put ative dopamine Dq receptor were assessed in sections of rat and human atria and ventricles using combined radioligand binding and autoradiog raphic techniques with [H-3]-spiperone as a ligand. 2 [H-3]-Spiperone was bound specifically to sections of human and rat atria and ventricl es. The binding was time-, temperature- and concentration-dependent, b elonging to a single class of high-affinity sites. In atria, the disso ciation 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 fm ol 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 th e B-max was 43.5 +/- 3.0 fmol mg(-1) tissue in rats and 56.4 +/- 3.2 f mol mg(-1) tissue in humans. 3 The pharmacological profile of [H-3]-sp iperone binding to sections of both rat and human atria and ventricles was consistent with the labelling of dopamine D-2-like receptors. [H- 3]-Spiperone binding was more sensitive to displacement by the neurole ptic clozapine in sections of atria than of ventricles, suggesting the expression of a dopamine D-4 receptor in atrial tissue. Moreover, pre incubation of some sections with a dopamine D-4 receptor antibody and subsequent exposure to [H-3]-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 autoradiogra phy revealed the accumulation of silver grains over atrial tissue with in atrial myocardiocytes. A higher density of silver grains was develo ped in rat than in human atria. In ventricles, silver grains were accu mulated primarily in cluster areas both in rats and in humans. 5 The a bove findings suggest the expression of a dopamine D-4 receptor in rat atria, but not in ventricles. A similar site was identified in human atria. The possible relevance of a dopamine D-4 receptor in the heart is discussed.