Comparison of the biological activity of pentagastrin, G-17 and G-34 on canine antral motility and intracellular electrical activity (Abstract)

Abstract

The intracellular microelectrode technique was used to determine the effects of pentagastrin, G-17 (synthetic human gastrin I) and G-34 (natural human G-34 I) on the electrical activity of single cells of the circular layer of canine antral muscles. Mechanical activity of the cells was simultaneously monitored by attaching a transducer to measure tension in the direction of the long axis of the circular fibres. The preparation measured approximately 2 × 7 mm. In this tissue, the action potential consists of an upstroke potential followed by a plateau potential. Changes in the strength of contraction are related to changes in the size of the plateau potential. All three forms of gastrin increased the action potential frequency and the amplitude and duration of the action potential plateau. Similarly, the frequency and force of contractions were increased. Dose-response curves for the effects on electrical activity were determined for single cells. The mean ED₅₀ for the effect of pentagastrin on plateau amplitude was 5 × 10⁻¹² ± 1.5 × 10⁻¹² M (n = 4) and on frequency was 5.5 × 10⁻¹⁰ ± 2.5 × 10⁻¹⁰ M (n = 3). G-17 was found to be slightly less potent, with ED₅₀ for plateau amplitude and frequency being 3.9 × 10⁻¹¹ ± 2.1 × 10⁻¹¹M (n = 4) and 2.0 × 10⁻⁹± 0.4 × 10⁻⁹M (n = 3), respectively. This difference in potency was confirmed by determining the dose-response curves for both agents in a single cell. Although there is a difference in potency, the comparison of both agents in a single cell indicates that the efficacies are similar. For both G-17 and pentagastrin, the effects on the size of the action potential plateau occurred in a lower concentration range than the effect on frequency. The effects on the plateau occur within the range of concentrations of gastrin present in the blood after a meal, whereas the effects on frequency are probably relevant only with respect to conditions of hypergastrinaemia. A sufficient quantity of G-34 was available for a single dose (3 × 10⁻¹⁰ M) but not for an entire dose-response curve. This dose was effective in increasing the size of the action potential plateau, action potential frequency, and the frequency and force of contraction. The effects of this dose were compared with the dose-response curve for G-17 obtained from the same cell. The results indicate that G-34 may have a greater biological activity than G-17 both on electrical and mechanical activity. We conclude that both G-17 and G-34 have physiological actions on canine gastric antral motility.