Kinetics of Atropine and Diamox Inhibition of Histamine-Stimulated Gastric Secretion

Abstract

Hirschowitz, B. I., Hutchison, G. A. & Sachs, G. Kinetics of atropine and diamox inhibition of histamine-stimulated gastric secretion. Scand. J. Gastroent. 1973, 8, 555-559.

Values for Vmax and Km were determined for histamine stimulation of gastric secretion in 7 conscious dogs with gastric fistula. Each dog had two control studies with a 7-dose, 45-minute step-increment infusion of histamine (HIST.) with a dose range of 2 to 150 μg base/kg. hr and one study each against a background of Diamox (D) (acetazolamide), 50 mg/kg, or atropine (A) 10 μg/kg. hr. Vmax values for volume were HIST. 106; HIST. + D, 35; HIST. + A, 116 ml/30 minutes, and Km values were HIST. 9.4; HIST. + D, 3.9 and HIST. + A 64 μg/kg. hr. Atropine inhibited competitively and Diamox uncompetitively. It is proposed that atropine acts on histamine-receptor binding and Diamox at the terminal step of H⁺ secretion, where the rate of H⁺ secretion quickly reaches the limits imposed by the uncatalyzed rate of hydration of CO₂ in the absence of carbonic anhydrase. We suggest that the latter reaction is limited by the supply of HCO₃^- to the HCO₃^- -stimulated transport ATPase, which is functionally dependent on carbonic anhydrase.

Key-words::

• Cl^-
• dogs
• gastric fistula
• gastric juice
• H⁺
• pepsin
• step dose histamine
• water