Pancreastatin: A novel peptide inhibitor of parietal cell secretion

Pancreastatin is a recently identified 49-amino-acid peptide found in gastrointestinal tract and gastric mucosa. Its biologic effects on gastric function are unknown. The aim of this study was to determine the effects of pancreastatin [33-49] (the synthetic C-terminal fragment) on acid secretion and somatostatin release in vitro. Isolated rabbit gastric glands were prepared by means of collagenase digestion. Acid secretion was assessed indirectly with use of ¹⁴C-aminopyrine (AP) uptake by glands, and somatostatin release from D cells was measured with radioimmunoassay. Pancreastatin alone (10^-10 to 10^-6 mol/L) had no effect on ¹⁴C-AP uptake compared with unstimulated glands. In contrast, pancreastatin inhibited with histamine-(10^-6, 10^-5 mol/L; p < 0.005) and carbachol-(10^-5, 10^-4 mol/L; p < 0.001) stimulated ¹⁴C-AP uptake in a dose-dependent manner. Neither forskolin-(10^-6, 10^-4 mol/L; p > 0.50) or 8-Br-cAMP-(10^-5, 10^-4 mol/L; p > 0.30) stimulated ¹⁴C-AP uptake were influenced by pancreastatin. Pancreastatin had no effect on somatostatin release from glands. These data suggest that pancreastatin probably acts at receptor or membrane level, inhibiting both histamine- and carbachol-stimulated ¹⁴C-AP uptake. These effects are not mediated by D cell somatostatin release. It is possible that pancreastatin acts as a paracrine or endocrine inhibitory regulator of parietal cell secretion.