Alpha‐Ketoglutarate Regulates Intestinal Motility and Health by OXGR1 in Nitrergic Neuron of Enteric Nervous System

ABSTRACT Intestinal health could be affected by intestinal motility, which is controlled by the enteric nervous system. In this study, we found that α‐ketoglutarate (AKG) inhibits intestinal motility and improves intestinal permeability, accompanied by an increased count of intestinal flora. We also identified that the AKG receptor, oxoglutarate receptor 1 (OXGR1), is expressed in the myenteric plexus (MP). Meanwhile, OXGR1 knockout enhanced intestinal motility. Furthermore, we found that AKG activates nitrergic neurons to synthesize nitric oxide through OXGR1, thereby suppressing intestinal smooth muscle contractility. Finally, we demonstrate that AKG/OXGR1 activates nitric oxide synthase in combination with calmodulin in nitrergic neurons. Taken together, this study may identify novel therapeutic targets for intestinal disease, such as diarrhea or colitis.