217 | Presynaptic voltage gated calcium channels are inhibited by glucagon like peptide 1 receptor (GLP-1R) and ghrelin receptor (GHSR) activity

Neural Circuits and Systems Neuroscience

Author: victoria pinto | Email: vicpinto98@gmail.com

Victoria Pinto , Julieta Aguggia  Silvia Rodriguez , Abdella Mohammed Habib , Jesica Raingo , Mario Perello

1° Instituto Multidisciplinario de Biología Celular (IMBICE)
2° College of Medicine, QU Health, Qatar University, Doha, Qatar

Anti-obesity therapies have the potential to improve quality of life of diabetic patients. In this context, the glucagon-like peptide-1 (GLP-1) is a multifaceted gastrointestinal hormone with a large therapeutic potential. GLP-1 receptor (GLP-1R) agonists, like Liraglutide, are commercially available drugs to treat both diabetes and obesity. Another gastrointestinal hormone implicated in food intake is ghrelin, which acts on its specific receptor (GHSR). GLP-1R and GHSR are both G protein coupled receptors (GPCR). We previously demonstrated that GHSR controls neuronal voltage gated calcium channels that control neurotransmitter release and that may contribute to its orexigenic effects. On the other hand, the molecular mechanism by which GLP-1 reduces food intake remains unclear. Here we found that increasing GLP-1R expression reduces CaV2.2 current in a heterologous expression system (GLP1-R plasmid added versus calcium current density linear regression R=0.07514 Slope=70.25 n=120) and that acute Liraglutide 0.2 µM application further reduces the current (current inhibition: 49.47±12,14 % n=4). Notably we observed co localization of GHSR and GLP1-R in brain areas that control food intake such as Lateral Parabrachial Nucleus: T thus we plan to study a putative crosstalk between the effect of these two relevant GPCRs at central level. This work is supported by a collaborative grant with Qatar University (NPRP13S-0209-200315)