Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats

The gastric exocrine inhibitory activities of somatostatin-28 (SS-28) and somatostatin-14 (SS-14) were determined in conscious cats prepared with gastric fistulae. Gastric acid and pepsin secretions were stimulated with pentagastrin. Expressed in terms of exogenous doses, SS-14 (ID₅₀: 1.49 nmol · kg^-1 · h^-1) was 3.4 times more potent than SS-28 (ID₅₀: 5.12 nmol · kg^-1 · h^-1) as an inhibitor of gastric acid secretion. Similarly SS-14 (ID₅₀: 0.25 nmol · kg^-1 · h^-1) was 3.8 times more potent than SS-28 (ID₅₀: 0.96 nmol · kg^-1 · h^-1) as an inhibitor of pepsin secretion. Expressed in terms of circulating plasma concentration measured by radioimmunoassay, SS-14 (ID₅₀: H⁺, 232 and pepsin 73 pM) was 8-9 times more potent than SS-28 (ID₅₀: H⁺, 2112 and pepsin, 611 pM) as an inhibitor of gastric exocrine secretions. The plasma immunoreactive half-life of SS-28 (6.1 min) was double that for SS-14 (2.4 min) possibly due to a slower theoretical metabolic clearance rate of the larger peptide (30 and 87 ml · kg^-1 · min^-1, respectively). Both peptides had similar apparent distribution volumes (SS-14, 306 and SS-28, 263 ml · kg^-1). As judged by gel chromatography of plasma samples, there was no evidence for the conversion of SS-28 to SS-14 in vivo. The reduced activity of SS-28, compared with SS-14, against gastric exocrine secretions contrasts with its more potent effects in the pituitary and pancreas.