Incremental and decremental kinetics of gastric responses to infused gastrin in dogs

Abstract

Acid and pepsin secretion was stimulated by graded doses of synthetic human gastrin I (G-17-I) and pentagastrin (G-5) in six conscious gastric fistula dogs, three with intact vagi and three with fundic vagotomy. Metabolic clearance rate of G-17 was 15.2 ml.kg-1.min-1 and volume of distribution was 15.8%. Gastrin levels decayed in two slopes: t1/2 of 6.8 min and 25-35 min, respectively. These were compared with other published data. Vmax was higher in intact stomachs and at doses or blood levels of gastrin about three to four times smaller. G-17 was almost four times more potent (molar basis) than G-5. Responses were log linearly related to G-17 dose and to serum G-17 during infusion (incremental) and after stopping infusion (decremental). Normalized decremental curves were congruent in all dogs but displaced fivefold (625 vs. 130 pmol/l) to the right at midpoint. Vagotomy changed only association (incremental) kinetics (Km = 352 pmol/l). The previously undescribed difference between blood concentration-effect relationship during drug administration and withdrawal may be important in situations in which blood levels are used as therapeutic guide.