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

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.