Stimulation of acid and pepsin secretion in the fistula dog by 4(5)-methyl histamine, a specific H-2 agonist

Abstract

4-Methyl histamine, a ring analog of histamine, is a specific agonist for the H-2 receptor of the gastric parietal cell. Gastric H⁺ and pepsin responses to graded doses of 4-methyl histamine [4(Me)H] and to histamine in fistula dogs show that pepsin is stimulated about 4–5 times more strongly by 4(Me)H but that for H⁺ secretion, time of onset (10–20 min), rate of reaching peak secretion (45–90 min), peak output (10 mEq/15 min), rate of fade (30% in 2 hours), the dose giving near-maximum response (100 μg/kg-hr), and kinetic parametersV_max (45 mEq/hr) andK _m (11.8 μg/kg-hr for 4(Me)H compared to 12.4 μg/kg-hr for histamine) do not serve to distinguish the two drugs with respect to the parietal cell. After infusion of 4(Me)H was stopped, H⁺ secretion declined exponentially with time, and the half-time of this slope was linearly proportional to dose. At all doses, this decay of response was several times slower than with histamine, representing the only difference from histamine as regards gastric acid secretion in the dog.