Neurohormonal regulation of ion transport in the porcine distal jejunum. Actions of somatostatin-14 and its natural and synthetic homologs

The tetradecapeptide somatostatin-14 (SS-14) has been found to alter electrogenic ion transport in the rat, guinea pig and rabbit intestinal mucosa in vitro. In this study, the actions of SS-14 and related peptides on mucosal ion transport were investigated in the intestinal tract of the pig, a species whose digestive physiology is similar to man. The contraluminal- but not luminal-side administration of SS-14 (1-1000 nmol/l) to sheets of mucosa-submucosa obtained from different regions of the porcine small intestine and colon produced rapid, sustained decreases in short-circuit current (Isc), a measure of active ion transport, that were localized to segments of the distal jejunum. The magnitude of this peptide action was greater in tissues manifesting a serosa-positive basal potential difference >0 mV than in those displaying a spontaneous potential difference <0 mV. Under basal conditions, SS-14 produced a maximum decrease in distal jejunal Isc which was nearly twice that produced by its synthetic analog SMS 201,995 (octreotide); the two peptides inhibited Isc with similar potencies. SS-14 (20 nmol/l) increased the lumen-toserosa transepithelial Cl flux and eliminated net residual flux. Mucosal Isc responses to SS-14 were absent in tissues bathed in HCO₃-free media. Peptide actions were generally resistant to inhibitors of epithelial anion exchange, Na-proton exchange and NaCl cotransport. The adenylate cyclase activator forskolin (1 μmol/l) and the cyclic AMP analog 8-bromo-cyclic AMP (0.3 mmol/l) evoked net Cl secretion which was associated with rapid and sustained elevations in Isc. Mucosal responses to these secretagogues were not affected by elimination of buffer HCO₃. SMS 201,995, SS-14 and its natural homolog, SS-28, decreased forskolin-stimulated Isc with respective EC₅₀s of 0.3, 6 and 16 nmol/l. At 10 nmol/l, SS-14 decreased Isc and net residual flux, but not net Na or Cl secretion induced by 8-bromo-cyclic AMP. Its effects were abolished by 0.1 μmol/l of contraluminal tetrodotoxin; the toxin alone decreased basal Isc, but did not alter mucosal Isc responses to secretagogues. SS-14 actions in the presence of forskolin were unaffected by phentolamine or naloxone administered at a contraluminal concentration (10 μmol/l) that inhibited the Isc-decreasing actions of epinephrine and [D-Ala², Met⁵]enkephalinamide, respectively. These results suggest that SS-14 and related peptides modify electrogenic ion transport in the porcine distal jejunum. Their actions, which appear to differ from those described previously in the rat and rabbit intestine, are mediated through receptors located on an unidentified subpopulation of enteric neurons.