Guanidinoacetate (GAA) is a potent GABAA receptor GABA mimetic: Implications for neurological disease pathology

Abstract: We show that GAA, γ-GBA, and GES share structural similarities with GABA, evoke GABAA receptor (GABAAR) mediated currents (whereas creatine [methylated GAA] and arginine failed to evoke discernible currents) in cerebellar granule cells in mouse brain slices and displace the high-affinity GABA-site radioligand[3H] muscimol in total brain homogenate GABAARs. We conclude that orthosteric activation of GABAARs by GAA, and potentially other GABAAR mimetic guanidino compounds (GCs) like γ-GBA and GES, interferes with normal inhibitory GABAergic neurotransmission which could mediate, and contribute to, neurotoxicity.

Link to article: https://onlinelibrary.wiley.com/doi/10.1111/jnc.15774

PubMed: https://pubmed.ncbi.nlm.nih.gov/36726215/

Authors: Pratap Meera, Mikko Uusi-Oukari, Martin Wallner, Gerald S. Lipshutz

Key Terms: GAMT, Basic science, Non-CCDS Diseases, General Creatine