The interplay between hydrogen ions, bicarbonate ions and osmolality in the anterior duodenum modulating gastric...

1. Gastric emptying, gastric acid and pepsinogen secretion were assessed simultaneously in the conscious calf using the test meal and duodenal perfusion technique (Bell & Mostaghni, 1975).2. Duodenal infusion of NaCl at a constant osmolality of 300 m-osmole/kg, but with pH ranging from 2.0 to 12.0, did not alter the high level of gastric emptying and secretion already reported for isotonic NaCl or NaHCO(3) alone (Bell & Mostaghni, 1975; Bell & Webber, 1979). Gastric function, therefore, is either unaffected by gastric chyme at pH 2.0-12.0 entering the duodenum, or else isotonicity is dominant over pH in activating duodenal receptors which increase motor activity.3. When the pH of the isotonic NaCl was reduced by the addition of HCl to below pH 2.0, inhibition of gastric function occurred in direct proportion to the amount of titratable acid present in the infusate. The H(+) moiety of isotonic duodenal infusates of pH < 2.0 dominates activation of osmoreceptors and so inhibits motor activity.4. When the same amount of acid but at differing concentrations and infusion rates was introduced into the duodenum uniform inhibition of gastric function occurred. This result indicates that duodenal acid receptors respond to acid concentration and flow rate to produce an integrated response in proportion to the amount (concentration x volume) of acid present.5. Isotonic NaHCO(3) solutions adjusted to pH 8.1-12.0 by the addition of NaOH, like isotonic NaCl infusions, did not affect gastric function until pH 11.0-12.0, when significant inhibition occurred. This inhibitory effect of isotonic NaHCO(3) at high pH is probably due to CO(3) (2-), since Na(2)CO(3) and Li(2)CO(3), but not LiCl, produce a similar inhibitory effect on gastric function.6. The inhibitory effect of carbonate gives some support to the existence of a CO(2)-sensor as suggested by Hunt & Knox (1972), whereby increased P(CO2) produced by intracellular or intercellular neutralization of CO(3) (2-) by duodenal H(+) activates acid receptors. But other experiments reported here, where simultaneous perfusion of HCl and excess NaHCO(3) produced a rise in intraluminal P(CO2), did not inhibit gastric function, which is contrary to the idea of a direct intraluminal effect of CO(2) on duodenal receptors.7. The pH, P(O2), P(CO2), HCO(3) (-) and base excess of venous blood showed no detectable change during duodenal infusion of either acidic or alkaline solutions. Metabolic acidosis or alkalosis, therefore, cannot be considered to play any part in controlling gastric function. The results thus corroborate the notion that the receptors controlling gastric function are localized in the intestinal mucosa.8. Our results suggest that interplay between acid and osmolality of gastric chyme occurs in the rostral part of the duodenum to produce a graded inhibitory effect which by negative feedback modulates the gastric effectors that normally activate smooth muscle, parietal cells and zymogen cells.