Mechanism of inhibition of gastric acid secretion by vagal denervation in the rat.

Acute bilateral subdiaphragmatic vagotomy in the conscious fistula rat greatly reduced gastric acid secretion, stimulated by the combined intravenous infusion of pentagastrin (10 micrograms/kg/h), histamine dihydrochloride (3 mg/kg/h) and carbachol (50 micrograms/kg/h). The reduction of acid output was immediate (within 15 min after vagotomy). The greatly reduced acid response to these secretagogues persisted for at least 8 weeks after vagal denervation (longest time studied). The sudden and dramatic effect of vagotomy on acid secretion is not related to a possible deficiency of either acetylcholine or histamine at the respective receptor site since the combined infusion of gastrin, histamine and carbachol did not prevent the suppression of acid secretion. Since the decline in acid output following vagal denervation was immediate, it probably reflects a sudden inaccessibility rather than loss of muscarinic or H2-receptors. The acid output obviously depends upon intramural "transducer" systems that respond to and transmit the vagal input. It is likely that the intramural ganglia represent such "transducer" systems. In the absence of a vagal drive these neuronal "transducers" cease to fire and as a result the parietal cells become almost unresponsive to stimuli.