Functional and autoradiographic characterization of dopamine D2-like receptors in the guinea pig heart

• Published in: Canadian journal of physiology and pharmacology 2002-06, Vol.80 (6), p.578-587
• Main Authors: Gómez, María de Jesús, Rousseau, Guy, Nadeau, Réginald, Berra, Roberto, Flores, Gonzalo, Suárez, Jorge
• Format: Article
• Language: English
• Subjects: Adenylyl Cyclases - metabolism; Animals; Autoradiography; Benzamides - metabolism; Biological and medical sciences; Blood Pressure - drug effects; Blotting, Western; Cyclic AMP - metabolism; Dopamine; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Electrophysiology; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Heart; Heart Rate - drug effects; In Vitro Techniques; Kinetics; Ligands; Male; Membranes - drug effects; Membranes - metabolism; Myocardium - cytology; Myocardium - metabolism; Raclopride - pharmacology; Receptors, Dopamine D2 - drug effects; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D2 - physiology; Receptors, Dopamine D3; Receptors, Dopamine D4; Tetrahydronaphthalenes - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y02-081

Dopamine receptors include the D 1 - (D 1 and D 5 subtypes) and D 2 -like (D 2 , D 3 , and D 4 subtypes) families. D 1 -like receptors are positively and D 2 -like receptors negatively coupled to the adenylyl cyclase. Dopamine D 2 -like (D 4 subtype) receptors have been identified in human and rat hearts. However the presence of D 2 and D 3 receptor subtypes is unclear. Furthermore, their role in cardiac functions is unknown. By autoradiographic studies of guinea pig hearts, we identified D 3 and D 4 receptors, using the selective radioligands [ 3 H]-7-OH-DPAT and [ 3 H]emonapride (YM-09151-2 plus raclopride). Western blot analysis confirmed D 3 and D 4 receptors in the right and left ventricle of the same species. Selective agonists of D 3 and D 4 receptors (±)-7-OH-DPAT and PD 168 077 (10 –9 to 10 –5 M, respectively) induced a significant negative chronotropic and inotropic effect in the isolated guinea pig heart preparation. Negative inotropic effect induced by PD 168 077 was associated with an inhibition in cyclase activity. No changes in cyclase activity were found with (±)-7-OH-DPAT. The aim of this study is to support the presence of D 3 and D 4 receptors in the heart. Although our results suggest that D 3 and D 4 receptors are functionally active in the heart, we need additional information with an antagonist and an agonist of improved potency and selectivity to understand the respective roles of D 3 and D 4 receptors in the cardiac functions.Key words: Dopamine receptors (D 2 , D 3 , D 4 subtypes), autoradiography, Western blot, cAMP, heart.