The appropriate expression of specific neurotransmitter receptors within the cellular networks that compose the enteric nervous system (ENS) is central to the regulation of gastrointestinal (GI) functions. While the ENS expression patterns of the neurotransmitter glutamate have been well documented, the localization of its receptors on ENS neurons remains to be fully characterized. We investigated the expression patterns of glutamate receptor AMPA subunits within ENS neurons of the mouse colon and the consequences of their pharmacological activation on spontaneous colonic contractility.Methods
RT-PCR was used to detect individual AMPA receptor (GluR 1-4) subunit expression at the mRNA level in mouse colon tissue. Immunohistochemistry and confocal microscopy was used to localize the expression of the GluR1 and 4 subunits in colon tissue. Brain tissue was used as a positive control. Organ bath preparations were used to determine the effect of AMPA receptors activation on the force and frequency of colonic longitudinal smooth muscle spontaneous contractions.Key Results
GluR1, 3, 4 mRNA was detected in the mouse colon. Immunoreactivity for GluR1 and 4 subunits was detected on the somatic and dendritic surfaces of subpopulations of neurochemically defined ENS neurons. The pharmacological activation of AMPA receptors increased the force but not frequency of spontaneous colonic contractions.Conclusions & Inferences
Molecularly distinct AMPA receptor subtypes are differentially expressed within the neural networks of the mouse colon and have a direct role in motility. These data provide the rationale for the development of AMPA-selective ligands for the therapeutic delivery to the GIT in motility disorders.
We investigated the expression of AMPA receptor subunits (GluR1-4) within the mouse colon and the effect of their pharmacological activation on spontaneous colonic contractions. RT-PCR analyses demonstrated that the GluR1, 3, 4 subunits were expressed in the colon at the mRNA levels; immunohistochemistry and confocal microscopy revealed that these subunits are expressed on neurochemically defined ENS neurons; and organ bath studies indicated that the pan-AMPA receptor activation increased the force but not frequency of spontaneous colonic contractions. The data suggest a central role for AMPA receptors in ENS neuronal excitability as well as glutamate-mediated GI contractility.