D1-dopamine receptors in the heart

• Applicant: Privatdozent Dr. Ulrich Gergs
• Subject Area: Pharmacology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519414516

Here, we want to investigate the functional and biochemical effects of human D1-dopamine receptors on the mammalian heart. The importance of the D1-dopamine receptor in the heart of humans and common experimental animals (guinea pigs, rabbits, mice, rats) is unclear. Possibly, the D1-dopamine receptor couples to a positive inotropic and a positive chronotropic effect, because the D1-dopamine receptor, like the β-adrenoceptor, can in principle activate the adenylyl cyclase via guanosine triphosphate-binding proteins that increases 3',5'-cyclic adenosine -monophosphate (cAMP) in the cardiac myocytes. The stimulation of the D1-dopamine receptor should also increase the atrioventricular conduction and probably also accelerate the generation of excitation in the sinus node. However, there are contradictory findings on the inotropic effect of D1-dopamine receptors: both, positive and negative inotropic effects but also missing inotropic effects have been reported in mammalian hearts. Dopamine, the eponymous ligand of the D1-dopamine receptor, can also stimulate β-adrenoceptors in the heart. With the present application, we want to close important gaps in the understanding of the human D1-dopamine receptor with a newly developed mouse model in which the human D1-dopamine receptor is overexpressed in cardiomyocytes. These findings should help to better understand the importance of the human D1-dopamine receptor in the human heart, which could lead to new therapeutic options in the treatment of heart failure in the long term.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Joachim Neumann