Atik, Hicham
[UCL]
Hermans, Emmanuel
[UCL]
The concept of “functional selectivity” points out that GPCRs exist in multiple active or inactive conformations that can be differentially stabilized by some specific ligands. Each active conformation promotes the preferential recruitment of a given signalling partner. High receptor density, putatively favouring the formation of homoreceptor complexes, has been reported to influence the coupling of signalling partners at the receptor. In a pharmacological perspective this offers the opportunity to more specifically manipulate receptor-associated responses, and in particular to reduce drug-induced side-effects. These concepts are of major importance in PD, as treatments supporting DA transmission at D2Rs are associated with side-effects, impairing the quality of life of patients. We therefore hypothesize that the increased density of D2R that characterize early stages of PD could promote the formation of homoreceptor complexes, and thereby alter the functional selectivity of clinically used D2R agonists such as pramipexole.
Bibliographic reference |
Atik, Hicham. Impact of dopamine receptor density on the formation of homoreceptor complexes and on the functional selectivity of agonists used in the treatment of Parkinson's disease. Faculté de pharmacie et sciences biomédicales, Université catholique de Louvain, 2021. Prom. : Hermans, Emmanuel. |
Permanent URL |
http://hdl.handle.net/2078.1/thesis:30885 |