The effect of somatostatin (SRIF) on ion transport was determined in the rat colon in vitro. SRIF produced a sustained decrease in the short circuit current (I[sc]) (-0.8 ± 0.1 μeq/h·cm2) and increased net Cl absorption (0.9 ± 0.3 μeq/h·cm2). The threshold effect of SRIF on I[sc] was observed at 6 nM. 10μM serotonin decreased net Na absorption (-2.6 ± 0.4 μeq/h·cm2), net Cl absorption (-3.6 ± 0.5 μeq/h·cm2) and increased I[sc] (0.7 ± 0.1 μeq/h·cm2); these changes were totally blocked by 0.1 μM SRIF. SRIF completely blocked net Cl secretion induced by 10 mM theophylline (-2.5 ± 0.7 to +4.1 ± 2.0 μeq/h·cm2) and partially blocked theophylline-induced inhibition of net Na absorption (0.7 ± 0.5 to 2.1 ± 0.4 μeq/h·cm2). SRIF also blocked prostaglandin E1 (PGE1) induced increase in potential difference and I[sc] (P < 0.001). Mucosal cyclic AMP levels were increased by theophylline and PGE1 but not by serotonin. SRIF had no effect on basal or theophylline- and PGE1-stimulated cyclic AMP levels. These results indicate that SRIF blocks both cyclic AMP and noncyclic AMP mediated changes in ion secretion and suggest that SRIF is acting at a step in the secretory process beyond the formation of cyclic AMP.
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