Glutamatergic functions of primary afferent neurons with special emphasis on vagal afferents

Glutamate has been identified as the main transmitter of primary afferent neurons. This was established based on biochemical, electrophysiological, and immunohistochemical data from studies on glutamatergic receptors and their agonists/antagonists. The availability of specific antibodies directed against glutamate and, more recently, vesicular glutamate transporters corroborated this and led to significant new discoveries. In particular, peripheral endings of various classes of afferents contain vesicular glutamate transporters, suggesting vesicular storage in and exocytotic release of glutamate from peripheral afferent endings. This suggests that autocrine mechanisms regulate sensory transduction processes. However, glutamate release from peripheral sensory terminals could also enable afferent neurons to influence various cells associated with them. This may be particularly relevant for vagal intraganglionic laminar endings, which could represent glutamatergic sensor-effector components of intramural reflex arcs in the gastrointestinal tract. Thus, morphological analysis of the relationships of putative glutamatergic primary afferents with associated tissues may direct forthcoming studies on their functions.