Somatostatin peptides prevent increased human colonic epithelial permeability induced by hypoxia.

Mesenteric ischemia increases gut permeability and bacterial translocation. In human colon, chemical hypoxia induced by 2,4-dinitrophenol (DNP) activates basolateral intermediate conductance K(+) (IK) channels (designated KCa3.1 or KCNN4) and increases paracellular shunt conductance/permeability (G(S)), but whether this leads to increased macromolecule permeability is unclear. Somatostatin (SOM) inhibits IK channels and prevents hypoxia-induced increases in G(S). Thus, we examined whether octreotide (OCT), a synthetic SOM analog, prevents hypoxia-induced increases G(S) in human colon and hypoxia-induced increases in total epithelial conductance (G(T)) and permeability to FITC-dextran 4000 (FITC) in rat colon. The effects of serosal SOM and OCT on increases in G(S) induced by 100 µM DNP were compared in isolated human colon. The effects of OCT on DNP-induced increases in G(T) and transepithelial FITC movement were evaluated in isolated rat distal colon. G(S) in DNP-treated human colon was 52% greater than in controls (P = 0.003). G(S) was similar when 2 µM SOM was added after or before DNP treatment, in both cases being less (P < 0.05) than with DNP alone. OCT (0.2 µM) was equally effective preventing hypoxia-induced increases in G(S), whether added after or before DNP treatment. In rat distal colon, DNP significantly increased G(T) by 18% (P = 0.016) and mucosa-to-serosa FITC movement by 43% (P = 0.01), and 0.2 µM OCT pretreatment completely prevented these changes. We conclude that OCT prevents hypoxia-induced increases in paracellular/macromolecule permeability and speculate that it may limit ischemia-induced gut hyperpermeability during abdominal surgery, thereby reducing bacterial/bacterial toxin translocation and sepsis.NEW & NOTEWORTHY Somatostatin (SOM, 2 µM) and octreotide (OCT, 0.2 µM, a long-acting synthetic analog of SOM) were equally effective in preventing chemical hypoxia-induced increases in paracellular shunt permeability/conductance in isolated human colon. In rat distal colon, chemical hypoxia significantly increased total epithelial conductance and transepithelial movement of FITC-dextran 4000, changes completely prevented by 0.2 µM OCT. OCT may prevent or limit gut ischemia during abdominal surgery, thereby decreasing the risk of bacterial/bacterial toxin translocation and sepsis.