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Autoradiographic localization of dopexamine binding sites and dopexamine‐sensitive cyclic adenosine monophosphate generating system in the rat heart
Author(s) -
Napoleone Paolo,
Cavallotti Carlo,
Strocchi Paola,
Ricci Alberto,
Amenta Francesco
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430250203
Subject(s) - antagonist , medicine , ventricle , sch 23390 , endocrinology , chemistry , adenosine , binding site , sulpiride , receptor , biophysics , biology , biochemistry
Abstract The present study was designed to analyze the pharmacological characteristics and the anatomical localization of ( 3 H)x‐dopexamine (DPX) in frozen sections of rat right and left ventricles. Moreover, the effect of DPX on 3′‐5′‐cyclic adenosine monophosphate (cAMP) generating system in membrane particles of rat left ventricle was investigated. ( 3 H)‐DPX was specifically bound by sections of rat right and left ventricles. The binding was time‐, concentration‐, and temperature‐dependent and reversible. The pharmacological profile of ( 3 H)‐DPX binding was consistent with the labeling of both β2‐adrenoceptors and DA2 receptors. In fact, the most potent displacer of ( 3 H)‐DPX binding was the β2‐adrenoceptor antagonist ICI 118,551, followed by L‐propranolol, dopamine, noradrenaline, and L‐sulpiride. The β1‐adrenoceptor antagonist metoprolol and the DA1 receptor antagonist SCH 23390, even at high concentrations, were without effect on ( 3 H)‐DPX binding. Autoradiography revealed a rather homogeneous distribution of ( 3 H)‐DPX binding sites within both right and left ventricles. ( 3 H)‐DPX is specifically bound by myocytes. The binding was antagonized primarily by ICI 118,551 and in lesser amounts by L‐sulpiride. ICI 118,551 and L‐sulpiride together reduced the density of silver grains to non‐specific binding. DPX dose‐dependently increased CAMP concentration in membrane particles of rat left ventricle. This effect was antagonized by ICI 11 8,551 but not by SCH 23390. The above data suggest that the cardiac actions of DPX are primarily mediated via an interaction with β2‐adrenoceptors. Moreover, a specific binding to DA2 receptors is also noticeable. The interaction with these different receptors most likely accounts for some of the cardiac effects of DPX.