In vitro effects of somatostatin on ion transport in rabbit intestine

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Abstract
Somatostatin (SRIF) caused a rapid decrease in short-circuit current (Isc) when added to rabbit ileal mucosa in vitro, a half-maximal effect being attained with 3.5 .times. 10-8 M. Except at very high concentration (10-5 M), the decrease in Isc reversed spontaneously, its duration varying directly with the dose added. Repeated additions of the same dose elicited progressively smaller responses, suggesting tachyphylaxis. The effects of SRIF on Isc, which resemble those caused by .alpha.-adrenergic agonists, were not reversed by phentolamine. SRIF (10-5 M) produced substantial (> 25 .mu.A/cm2) decreases in Isc in ileal mucosa from only about half of the rabbits tested. Initially, these responders had higher values for Isc, lower net Na and Cl fluxes, and larger residual ion fluxes (Isc-net Na flux + net Cl flux) than did nonresponders. SRIF modified ion transport only in responders, equalizing fluxes between the 2 groups. SRIF failed to decrease Isc when added to gastric antral, duodenal, jejunal or colonic mucosa and had no effect on Na and Cl fluxes across jejunal mucosa. SRIF (10-6 M) did not alter the increases in Isc produced by the following secretagogues: theophylline, 8-bromo-c[cyclic]AMP, 16,16-dimethyl prostaglandin E2 (dM-PGE2), vasoactive intestinal peptide (VIP), heat-stable Escherichia coli enterotoxin (ST) and Ca ionophore A23187 [2-[(3.beta.,9.alpha.,11.beta.-trimethyl)-8-(2-pyrrole carboxymethyl)-1,7-dioxaspiro[6.6] undecyl-2.beta.-methyl]-5-methyl aminobenzoxazole-4-carboxylic acid]. SRIF did reduce by 40% the Isc response to carbamylcholine. Na and Cl flux measurements in the presence and absence of dM-PGE2 and/or SRIF indicated that fluxes in the presence of both agents are the average of fluxes obtained with each agent separately. SRIF (10-6 M) had no effect on ileal mucosal cAMP and cGMP concentrations either in the absence of secretagogues or in the presence of VIP, dM-PGE2, or ST. SRIF stimulates NaCl absorption and inhibits the HCO3 secretion in rabbit ileum, thereby resembling the action of .alpha.-adrenergic agonists. It does not change cAMP or cGMP concentration; SRIF inhibits the response to cholinergic agonists but not other secretagogues.