Astrocytic NCS-382-insensitive gamma-hydroxybutyrate receptor

The Astrocytic NCS-382-insensitive gamma-hydroxybutyrate receptor is a putative signaling protein located on astrocytes that mediates cellular responses to gamma-hydroxybutyrate (GHB) (Le Meur et al., 2007). This target is characterized by its lack of inhibition by the classical GHB receptor antagonist NCS-382 and its independence from GABA-B receptor signaling (Maitre et al., 2016). Activation of this receptor by GHB triggers significant intracellular calcium transients within astrocytes, likely through a G-protein-coupled mechanism involving phospholipase C (Kemmel et al., 2010). These calcium signals are thought to facilitate the release of gliotransmitters such as glutamate or ATP, which in turn modulate neuronal activity and synaptic transmission (Bay et al., 2014). While the specific gene encoding this receptor has not yet been identified, it is considered a distinct pharmacological entity from the high-affinity GHB binding sites found on neurons. This target is relevant to the therapeutic effects of sodium oxybate, used in treating narcolepsy and alcohol withdrawal, and may play a role in the drug's neuroprotective properties (Gomes & Shen, 2021). However, the lack of a cloned sequence remains a challenge for precise drug targeting and molecular validation.

Other names

NCS-382-insensitive GHB binding sitePutative astrocytic GHB receptorNon-GABA non-GHB-receptor astrocytic target

Agonism of a putative G protein-coupled receptor on astrocytes, leading to the activation of the phospholipase C pathway and subsequent release of calcium from intracellular stores (Le Meur et al., 2007; Kemmel et al., 2010).