The role of somatostatin-14 in duodenal mucosal HCO3- secretion was investigated in anesthetized, indomethacin-treated guinea pigs. Net HCO3- 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 HCO3- secretion (3.5±0.2 μmol/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 HCO3- 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 HCO3- secretion, and its mechanism of action is not via inhibition of adenylate cyclase activity in duodenal enterocytes.
- adenylate cyclase
- prostaglandin E
- vasoactive intestinal peptide
ASJC Scopus subject areas