Effect of sorbin on electrolyte transport in rat and human intestine

Abstract

Stimulating water absorption in the colon represents an important target to reduce stool output in secretory diarrhea. Recently, a 153-amino-acid peptide was isolated from porcine upper small intestine and purified, taking into account the increase of water absorption in guinea pig gallbladder. Accordingly, this peptide was named sorbin. The aim of the present study was to determine if the COOH-terminal heptapeptide of sorbin (C7-sorbin) participates in the regulation of electrolyte transport in the colon. Different regions (from duodenum to colon) of stripped intestinal mucosa from rats or humans were mounted in Ussing chambers to measure the changes in short-circuit current (Δ Isc) and net22Na and36Cl fluxes ([Formula: see text] and[Formula: see text]) after serosal exposure of 10−7to 10−3M C7-sorbin. In fasted rat intestine, C7-sorbin (10−4M) induced an immediate reduction in Iscin the distal ileum and proximal and distal colon but not in the duodenum and jejunum. In the colon, Iscreduction and[Formula: see text] and[Formula: see text] stimulation were dose dependent (EC50= 2 × 10−5M). At 10−3M, maximal effect was observed (Δ Isc= −1.14 ± 0.05, Δ[Formula: see text] = +4.97 ± 1.38, and Δ[Formula: see text] = +9.25 ± 1.44 μeq ⋅ h−1⋅ cm−2). C7-sorbin (10−3M) inhibited the increase in Iscinduced by a series of 10 secretory agents such as secretin, vasoactive intestinal peptide, PGE2, and serotonin. In HT-29-Cl19A cells, C7-sorbin induced an increase in Isc, with a maximal effect at 10−3M (Δ Isc= 0.29 ± 0.10 μeq ⋅ h−1⋅ cm−2). In human intestine, a dose-dependent decrease in Iscwas observed in right and sigmoid colons in basal and stimulated conditions (EC50≅ 10−5M; at 10−4M, Δ Isc= −2.66 ± 0.17 μeq ⋅ h−1⋅ cm−2) but not in the jejunum. The results indicate that C7-sorbin stimulated NaCl neutral absorption and inhibited electrogenic Cl−in rat and human intestinal epithelia. In addition, the antisecretory effect was essentially observed in the distal part of both rat and human intestine and the magnitude of the proabsorptive effect was directly related to the magnitude of the previously induced secretion.