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 (lsc), 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 serosapositive basal potential difference greater than 0 mV than in those displaying a spontaneous potential difference less than 0 mV. Under basal conditions, SS-14 produced a maximum decrease in distal jejunal lsc which was nearly twice that produced by its synthetic analog SMS 201,995 (octreotide); the two peptides inhibited lsc with similar potencies. SS-14 (10 nmol/l) increased the lumen-to-serosa transepithelial Cl flux and eliminated net residual flux. Mucosal lsc 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 mumol/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 lsc.(ABSTRACT TRUNCATED AT 250 WORDS)