title: 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.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Institute of Laboratory Medicine, Lund University Hospital, S-22185 Lund, Sweden. per.norlen@skane.se
authors.forename: P
authors.initials: P
authors.lastname: Norlén
authors.forename: P
authors.initials: P
authors.lastname: Ericsson
authors.forename: M
authors.initials: M
authors.lastname: Kitano
authors.forename: M
authors.initials: M
authors.lastname: Ekelund
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019861:Enterochromaffin-like Cells / Q000187:drug effects / Q000502:physiology*; D005755:Gastrins / Q000494:pharmacology*; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D005755:Gastrins; D006632:Histamine
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