Effect of somatostatin-14 on duodenal mucosal bicarbonate secretion in guinea pigs

Abstract

The role of somatostatin-14 in duodenal mucosal HCO ₃ ⁻ secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO ₃ ⁻ output from the isolated, perfused (24 mM NaHCO₃ + 130 mM NaCl) proximal duodenum was measured during intravenous infusion (alone or in combination) of somatostatin-14, carbachol, vasoactive intestinal peptide (VIP), and prostaglandin E₂ (PGE₂). In homogenates of duodenal enterocytes, the effect of these agents on adenylate cyclase activity was studied. Basal duodenal HCO ₃ ⁻ secretion (3.5±0.2µmol/cm/10 min) was reduced dose dependently by somatostatin-14 (10⁻¹¹ mol/kg, 10⁻⁹ mol/kg, and 10⁻⁷ mol/kg). Carbachol, VIP, and PGE₂ (all 10⁻⁸ mol/kg) increased basal duodenal HCO ₃ ⁻ secretion two- to threefold. Somatostatin-14 (10⁻⁷ mol/kg) abolished the stimulatory effect of carbachol and VIP, but not that of PGE₂. Basal adenylate cyclase activity in isolated duodenal enterocytes (9.4±1.0 pmol cAMP/mg protein/min) was unaltered by somatostatin (10⁻⁶ mol/liter) or carbachol (10⁻³ mol/liter). VIP (10⁻⁸ mol/liter) and PGE₂ (10⁻⁷ mol/liter) increased adenylate cyclase activity two- to threefold, and these effects were unchanged by somatostatin-14 (10⁻⁶ mol/liter). In conclusion, somatostatin-14 inhibits basal and carbachol- and VIP-stimulated duodenal HCO ₃ ⁻ secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.