The characteristics of gastrin-stimulated gastric acid secretion were investigated in conscious cats fitted with chronic cannulated gastric fistulae, with particular reference to tachyphylaxis. 2. There is a significant postive correlation between the peak acid secretion in response to pentagastrin 8 microgram kg-1 hr-1 and body weight. Male cats secret significantly greater amounts of acid in response to pentagastrin than females. The difference is lessened, but not eliminated, by expressing the acid out put in terms of body weight. 3. Pentagastrin stimulates a dose-dependent increase in acid secretion in the range 0.5-32 microgram kg-1 hr-1 when the response to each dose is assayed on separate occasions. Pentagastrin 64 microgram kg-1 hr-1 does not produce a further increase in acid secretion. The acid response to pentagastrin 1-16 microgram kg-1 hr-1 assayed on a single occasion by a continuous infusion method shows a dose-response relationship up to 8 microgram kg-1 hr-1 when it reaches a plateau of secretion. There is no difference between the two methods of assaying the gastric acid stimulating activity using doses of pentagastrin up to 8 microgram kg-1 hr-1. 4 The acid secretion in response to pentagastrin 8 microgram kg-1 hr-1 reaches a maximum after 45 min of stimulation and thereafter shows tachyphylaxis. Over a period of 5 hr there are at least two phases of tachyphylaxis distinguishable. During the period 0.75--2.5 hr of stimulation there is a fast phase of tachyphylaxis (-32.0 muequivH+kg-1 15 min-1). This is followed by a slow phase of tachyphylaxis (-9.4 muequivH+kg-1 15 min-1) up to 5 hr of stimulation. 5. The absolute rate of the fast phase of tachyphylaxis of acid secretion (muequivH+kg-1 15 min-1) increases with increasing doses of pentagastrin, but rates of tachyphylaxis are similar when expressed as a percentage of the peak acid response to the particular dose of pentagastrin (5.1--7.8% 15 min-1). Synthetic human gastrin-17, the synthetic C-terminal decapeptide of human gastrin and the C-terminal tetrapeptide of gastrin have comparable rates of tachyphylaxis. The possible receptor models for the tachyphylaxis of gastrin-stimulated acid secretion are discussed.
