title: Gastrin release: Antrum microdialysis reveals a complex neural control.
abstract: We used microdialysis to monitor local gastrin release in response to food, acid blockade and acute vagal excitation. For the first time, gastrin release has been monitored continuously in intact conscious rats in a physiologically relevant experimental setting in a fashion that minimizes confounding systemic effects. Microdialysis probes were placed in the submucosa on either side of the antrum, 3 days before the experiments. The concentration of gastrin in the antral submucosal compartment was about 20 times higher than in the microdialysate and estimated to be 5-10 times higher than in serum regardless of the prandial state. The rats were conscious during microdialysis except when subjected to electrical vagal stimulation. Acid blockade (omeprazole treatment of freely fed rats for 4 days), or bilateral sectioning of the abdominal vagal trunks (fasted, 3 days post-op.), raised the gastrin concentration in blood as well as microdialysate. The high gastrin concentration following omeprazole treatment was not affected by vagotomy. Vagal excitation stimulated the G cells: electrical vagal stimulation and pylorus ligation (fasted rats) raised the gastrin concentration transiently in both serum and microdialysate. Food intake induced a 2- to 3-fold increase in serum gastrin, while gastrin in antral microdialysate increased 10- to 15-fold. In unilaterally vagotomized rats (fasted, 3 days post-op.), food evoked a prompt peak gastrin release followed by a gradual decline on the intact side. On the vagotomized side of the antrum, the peak response seemed to be reduced while the microdialysate gastrin concentration remained elevated. Thus, unilateral vagotomy surprisingly raised the integrated gastrin response to food on the denervated side compared to the intact side, indicating that vagotomy suppresses an inhibitory as well as a stimulating effect on the G cells. While local infusion of atropine was without effect, infusion of the neuronal blocker tetrodotoxin (TTX) (which had no effect on basal gastrin) virtually abolished the food-evoked gastrin response and lowered the high microdialysate gastrin concentration in omeprazole-treated rats by 65%. We conclude that activated gastrin release, unlike basal gastrin release, is highly dependent on a neural input: 1) Vagal excitation has a transient stimulating effect on the G cells. The transient nature of the response suggests that the vagus has not only a prompt stimulatory but also a slow inhibitory effect on gastrin release. 2) Although vagal denervation did not affect the gastrin response to anacidity, the TTX experiments revealed that both food-evoked and anacidity-evoked gastrin release depends on neural input.
authors.affiliation: Experimental and Clinical Pharmacology, Department of Laboratory Medicine, Lund University Hospital, S-221 85 Lund, Sweden. peter.ericsson@med.lu.se
authors.forename: P
authors.initials: P
authors.lastname: Ericsson
authors.forename: R
authors.initials: R
authors.lastname: Håkanson
authors.forename: J F
authors.initials: JF
authors.lastname: Rehfeld
authors.forename: P
authors.initials: P
authors.lastname: Norlén
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D005215:Fasting; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D005755:Gastrins / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology* / Q000601:surgery
chemical_list: D000897:Anti-Ulcer Agents; D005755:Gastrins; D013779:Tetrodotoxin; D009853:Omeprazole