Glutamate receptors in the stomach and their implications

Excitatory amino acids (EAAs), for example, L-glutamate (L-G1U) and L-aspartate (L-Asp), are present in various parts of the vertebrate central nervous system (CNS) and serve as major excitatory neurotransmitters (Bowman and Kimelberg, 1984; Marmo, 1988; Monaghan et a/., 1989; Gasic, 1995; Aschner et al., 2001). EAAs play important roles in many nervous systems including the gastrointestinal tract (Tsai et al., 199A, 1999; Kirchgessner et al., 1991 \ Liu et al., 1997). The glutamate receptors have been shown to be present in the submucous and myenteric plexuses (Liu et al, 1997; Liu and Kirchgessner, 2000; Reis et al., 2000; Ren et al., 2000). Several lines of evidence indicate a role of EAAs in the regulation of gastric motility, secretion, and gastric reflexes. However, the receptor subtypes and mechanisms that mediate the effects of EAAs in the stomach are still poorly understood. In the last few years, investigators have demonstrated that in addition to ionotropic glutamate receptors (iOluR), the enteric nervous system (ENS) also contains functional group I metabotropic glutamate (mOluR) receptors that appear to participate in enteric reflexes. These findings open up an entirely new area to study the roles of EAAs in gastric function and present potential new target sites for drug development.