Comparison of the step-dose and single-dose acid response to histamine and pentagastrin in chronic gastric fistula rats.

Time-response and dose-response curves for acid output to continuous infusion of histamine (HIST) and pentagastrin (PG) were determined by two techniques in conscious rats provided with chronic gastric fistula. With the step-dose technique the dose of the stimulant was increased each hour; with the single-dose technique only one dose of the stimulant was administered on each test day. The observed maximum acid output (OMAO) was obtained either by infusion of PG at a rate of 6 microgram/kg/h using both techniques or HIST at a rate of 1 mg/kg/h with the single-dose and 2 mg/kg/h with the step-dose technique. These OMAO were in the order: single PG greater than single HIST greater than step Hist greater than step PG in ratios 100--99--83--82. The dose-response curves were also analyzed by application of the Michaelis-Menten equation. For each stimulant there was no difference between the calculated maximum acid output (CMAO) whatever the technique used, but PG gave lower CMAO than HIST (p less than 0.05). For both stimulants the calculated doses for half the calculated maximal response (CD 50) are significantly higher with the step-dose than with the single-dose technique. These results are compared with those previously described in the literature for cats, dogs and man.