Radioligand binding and autoradiographic analysis of dopamine receptors in the human heart.

Abstract

The effects of dopamine on the 3',5-'cyclic adenosine monophosphate (cAMP) generating system were analyzed in membrane particles from the human right and left cardiac ventricle. In addition, the pharmacological profile and the anatomical localization of dopamine receptors were assessed on frozen sections of human cardiac atrial or ventricular tissue. Dopamine increased cAMP levels, in a concentration-dependent manner, in membranes of the right and the left ventricle. These effects were abolished by the beta-adrenoceptor antagonist (-)-propranolol, but not by the D1 receptor antagonist SCH 23390 or by the non selective D1/D2 receptor antagonist haloperidol. No specific binding of the D1 receptor antagonist [3H]-SCH 23390 was noticeable within the atrial or ventricular portions of the heart examined using either radioligand binding or autoradiographic techniques. The D2 receptor antagonist [3H]-spiroperidol, in the presence of concentrations of ketanserin sufficient to block possible binding to 5-HT2 sites, was specifically bound to sections of human heart with a dissociation constant value of about 2.6 nmol/l. The highest density of [3H]-spiroperidol binding occurred in the right ventricle followed, in descending order, by the right atrium, the upper part of the left ventricle, the lower part of the left ventricle, the left atrium and the interventricular septum. The binding profile of [3H]-spiroperidol to sections of human heart was consistent with the labeling of dopamine D2 sites. Light microscope autoradiography revealed silver grains throughout the atrial and ventricular walls and these were frequently accumulated in clusters.(ABSTRACT TRUNCATED AT 250 WORDS)