Exendin (5-39)

Exendin (5-39) is a selective GLP-1 receptor antagonist used to investigate endogenous glucagon-like peptide-1 signaling. By blocking the GLP-1 receptor, this compound attenuates the anorexigenic effects of GLP-1 and can enhance food intake under ad libitum conditions in certain models. Additionally, chronic administration of exendin (5-39) increases GLT-1 protein levels and glutamate uptake in the hippocampus, leading to decreased fEPSP decay time and inhibited long-term depression in the dentate gyrus. This makes it a valuable tool for studying GLP-1’s role in feeding behavior and its modulation of synaptic transmission and plasticity via astrocytic glutamate transport.

Intracerebroventricular administration of Exendin (5-39) at a dosage of 0.3 μg once daily for a week in male Wistar rats significantly augmented GLT-1 protein levels in the hippocampus. Additionally, hippocampal slices from Exendin (5-39)-treated or vehicle-treated rats demonstrated a decrease in fEPSP decay time, an enhancement in the input-output relationship, and a reduction in the paired-pulse ratio within the dentate gyrus (DG). Moreover, Exendin (5-39) was observed to inhibit long-term depression, albeit without affecting long-term potentiation in the DG. This effect was examined using an animal model comprising Wistar rats aged three weeks and those 18 days into pregnancy, underscoring Exendin (5-39)'s impact on hippocampal synaptic functions.