The Inhibitory Effect of 15(R) 15 Methyl Prostaglandin E₂ and the Interaction with Atropine on Stimulated Gastric Acid Secretion in Man

Abstract

The inhibitory effect of 15(R)15 methyl prostaglandin E₂ (Me PGE₂) on the gastric acid response to pentagastrin stimulation, 0.6 μg - kg⁻¹ h⁻¹, was examined in healthy male volunteers. Each subject underwent a control test and tests with intragastrically administered graded doses of 15(R)15 Me PGE₂ as free acid (80, 140, 200, and 400 μg, n = 5) and as methylester (80, 140, and 200 μg, n = 6). The percentage inhibition of the acid output during 2 h after increasing doses of the free acid was 24 ± 11, 49 ± 7, 44 ± 9, and 76 ± 12%. Corresponding figures for the methylester were 35 ± 2, 54 ± 5, and 64 ± 8%. Both volume and acidity were reduced. Side effects did not occur, except for moderate diarrhoea in one subject after 400 μg of the free acid. In a third series (n = 6) the combined effect of 80 μg methyl ester (44 ± 5% inhibition) and 1.5 mg atropine sulphate was studied. Atropine alone gave a 43 ± 6% inhibition by lowering the secreted volumes. For the combination the inhibition was 82 ± 3%. Intragastric 15(R)15 Me PGE₂ inhibited dose-dependently the pentagastrin-stimulated gastric acid response. Differences between the free acid and methyl ester of the analogue were not significant. Compared with other Me PGE₂ compounds, 15(R)15 Me PGE₂ was less effective per dose, but the dose range was broader and side effects were slight. Concomitantly given atropine had a significant additive inhibitory effect.

Key-words:

• Acid secretion
• prostaglandins
• stomach