Gastric Acid Secretion in the Totally Isolated, Vascularly Perfused Rat Stomach: A Selective Muscarinic-1 Agent Does, Whereas Gastrin Does Not, Augment Maximal Histamine-Stimulated Acid Secretion

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Abstract
The gastric acid secretion in response to graded doses of gastrin, histamine, impro-midine (a selective H2-receptor agonist), and the muscarinic-1 agonist McN-A-343 was studied in the totally isolated, vascularly perfused rat stomach. Combinations of stimulants at doses giving maximal acid secretion for each secretatogue were thereafter tested. All stimulants increased the gastric acid output significantly compared with the base-line output (7.2 ± 2.0 µeq/h). Gastrin induced significant increases in acid outputs at very low and physiologically relevant concentrations with a threshold concentration of 65 pM. Nevertheless, maximal gastrin-stimulated acid secretion represented only 55% of the maximal histamine-stimulated acid output of 154.8 ±±±± 10.0 ueq/h. Impromidine and McN-A-343 induced at maximum 59% and 34% of maximal histamine-stimulated acid output, respectively. Adding gastrin to the maximal histamine of impromidine-stimulated stomachs did not increase the acid secretion further. Histamine and McN-A-343 in combination, however, induced a more than additive increase in the gastric acid output (232.0 ± 14.7 µeq/h) than did histamine and McN-A-343 separately (154.8 × 10.0 and 53,0 ± 6.7µeq/h, respectively). The results indicate that in the rat, gastrin stimulates the parietal cell indirectly via histamine release, whereas muscarinic agents (cholinergic stimulation) act directly via a separate receptor.