AJP - Gastrointestinal and Liver Physiology, Vol 242, Issue 6 660-G667, Copyright © 1982 by American Physiological Society
Incremental and decremental kinetics of gastric responses to infused gastrin in dogs
B. I. Hirschowitz
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.
