D-Serine agonism of GluN1-GluN3 NMDA receptors regulates the activity of enteric neurons and coordinates gut motility.

ABSTRACT: The enteric nervous system (ENS) is a complex network of diverse molecularly defined classes of neurons embedded in the gastrointestinal wall and responsible for controlling the major functions of the gut. As in the central nervous system, the vast array of ENS neurons is interconnected by chemical synapses. Despite several studies reporting the expression of ionotropic glutamate receptors in the ENS, their roles in the gut remain elusive. Here, by using an array of immunohistochemistry, molecular profiling and functional assays, we uncover a new role for d-serine (d-Ser) and non-conventional GluN1-GluN3 N-methyl d-aspartate receptors (NMDARs) in regulating ENS functions. We demonstrate that d-Ser is produced by serine racemase (SR) expressed in enteric neurons. By using both in situ

SUBMITTER: Osorio N 

PROVIDER: S-EPMC10153202 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature