Step-Dose Compared to Separate-Dose Response Gastric Secretion with Histamine and Pentagastrin in Dogs — A Kinetic Analysis

Abstract

Hirschowitz, B. I. & Hutchison, G. Step-dose compared to separate-dose response gastric secretion with histamine and pentagastrin in dogs – a kinetic analysis. Scand. J. Gastroent. 1974, 9, 207-217.

In 7 fistula dogs, gastric juice volume, H, Cl, Na, K, and pepsin secreted in response to graded doses of histamine in 8 separate single doses (HIST.) (2-125 μg/kg • hr) and in 7 incremental 45-minute steps (2-150 μg/kg • hr) on the same day (STEPHIST.) were compared to the dose responses with pentagastrin also given in 7 single separate doses (PG) (.1-6 μg/kg • hr) and in 6 incremental 45-minute steps (.1 to 5 μg/kg • hr) (STEPPG.). Kinetic analysis using an exponential model (V = Vmax - be^-cs, where S = dose) gave Vmax, Km, and threshold each ± S.D. for each constituent. For H⁺ output Vmax ratios were in the order PG > HIST > STEPHIST > STEPPG 100:99:92:80, the latter being significantly less than the others presumably due to fade with pentagastrin. Values for volume, Cl, Na, and K were similarly ranked and were thus predictably affected by each drug and each mode of administration. Km values for mean output curves were STEPHIST > HIST > PG > STEPPG in molar ratio 100:50:0.7:0.35. Pepsin was dose responsively stimulated by pentagastrin but not by histamine. It was not possible to extract out of the single-dose experiments data which would reconstruct the step-dose responses, either by using comparable time periods or prior comparable H and electrolyte loss. Nevertheless the shorter step-dose technique, with certain provisos and corrections, is appropriate for comparing and characterizing drugs acting on gastric secretion and to describe the stomach being studied.

Key-words::

• Animal experiments
• dogs
• electrolytes
• gastric juice
• gastric secretion
• Km
• pepsin
• threshold
• Vmax