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1 Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga, Japan
2 Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
* To whom correspondence should be addressed. E-mail: fujimiya{at}belle.shiga-med.ac.jp.
We examined c-fos expression in specific brain nuclei in response to gastric distention, and investigated whether serotonin (5-HT) released from enterochromaffin (EC) cells was involved in this response. The role of 5-HT3 receptors in this mechanism was also addressed. The release of 5-HT was examined in an ex-vivo perfused stomach model, while c-fos expression in brain nuclei induced by gastric distention was examined in a freely moving conscious rat model. Physiological levels of gastric distention stimulated the vascular release of 5-HT more than the luminal release of 5-HT, and induced c-fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus (PVN) and supraoptic nucleus (SON). C-fos expression in all these brain nuclei was blocked by truncal vagotomy as well as by perivagal capsaicin treatment, suggesting that vagal afferent pathways may mediate this response. Intravenous injection of 5-HT3 receptor antagonist granisetron blocked c-fos expression in all brain nuclei examined, although intracerebroventricular injection of granisetron had no effect, suggesting that 5-HT released from the stomach may activate 5-HT3 receptors located in the peripheral vagal afferent nerve terminals and then induce brain c-fos expression. C-fos positive cells in the NTS were labeled with retrograde tracer fluorogold injected in the PVN, suggesting that neurons in the NTS activated by gastric distention project axons to the PVN. The present results suggest that gastric distention stimulates 5-HT release from the EC cells and the released 5-HT may activate 5-HT3 receptors located on the vagal afferent nerve terminals in the gastric wall leading to neuron activation in the NTS and AP, and subsequent activation of neurons in the PVN and SON.
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