The vagus regulates histamine mobilization from rat stomach ECL cells by controlling their sensitivity to gastrin

Abstract

The ECL cells in the oxyntic mucosa secrete histamine in response to gastrin, stimulating parietal cells to produce acid. Do they also operate under nervous control? The present study examines histamine mobilization from rat stomach ECL cells in situ in response to acute vagal excitation and to food or gastrin following vagal or sympathetic denervation. Applying the technique of microdialysis, we monitored the release of histamine by radioimmunoassay. Microdialysis probes were placed in the submucosa on either side of the stomach, 3 days before experiments. The rats were awake during microdialysis except when subjected to electrical vagal stimulation. One-sided electrical vagal stimulation raised serum gastrin and mobilized gastric histamine. However, gastrin receptor blockade prevented the histamine mobilization, indicating that circulating gastrin accounts for the response. Vagal excitation by hypoglycaemia (insulin) or pylorus ligation did not mobilize either gastrin or histamine. The histamine response to food was almost abolished by gastrin receptor blockade, and it was halved on the denervated side after unilateral subdiaphragmatic vagotomy. While the histamine response to a near-maximally effective dose of gastrin was unaffected by vagotomy, the response to low gastrin doses was reduced significantly. Abdominal ganglionic sympathectomy failed to affect the histamine response to either food or gastrin. In conclusion, gastrin is responsible for most of the food-evoked mobilization of ECL-cell histamine. The histamine response to electrical vagal stimulation reflects the effect of circulating gastrin rather than a direct action of the vagus on the ECL cells. Vagal denervation was accompanied by an impaired histamine response to food intake, probably reflecting the right-ward shift of the serum gastrin concentration-histamine response curve. The results suggest that the vagus controls the sensitivity of the ECL cells to gastrin.

The regulation of gastric acid secretion – clinical perspectives

“…It is firmly established that acetylcholine from the vagal nerves stimulates the parietal cells via a M3 receptor (Pfeiffer et al 1990). Neither the cholinergic agent carbachol (Sandvik et al 1998) nor electrical vagal stimulation (Norlen et al 2005) releases histamine directly. However, vagal electrical stimulation releases gastrin, which subsequently stimulates histamine release from the ECL cell (Norlen et al 2005).…”

“…) nor electrical vagal stimulation (Norlen et al . ) releases histamine directly. However, vagal electrical stimulation releases gastrin, which subsequently stimulates histamine release from the ECL cell (Norlen et al .…”

“…), a cell where vagal stimulation had been reported to exert no or marginal effect on the function, that is, histamine release (Norlen et al . ). Studying the effect of unilateral vagotomy in Japanese cotton rats, an animal spontaneously developing gastric carcinomas of ECL cell type (Martinsen et al .…”

High gastrin cell activity and low ghrelin cell activity in high-anxiety Wistar Kyoto rats

“…Although not statistically significant, the HDC activity tended to be lower in fed SPD rats than in fed WKY rats, suggesting that perhaps additional factors are required for gastrin to exert maximal effects in the oxyntic mucosa and that these factors may be lacking in WKY rats. Gastrin acts synergistically with the vagus in the trophic control of the rat oxyntic mucosa, and the ECL cells represent an important target for both gastrin and the vagus (Axelson et al 1988, Norlén et al 2005 indicating that they most likely also operate under nervous control.…”

Gastric secretions affected by esophageal distention in the rat

“…15 In other experiments, acid output was stimulated by insulin (0.6 IU/kg, 0.5 ml, i.p.) 16 or pentagastrin (20 μg/kg, 0.75 ml, i.p.). 17 Gastric pepsin secretion was stimulated by carbachol (20 μg/kg, i.p.).…”