Effects of inflammatory mediators on electrolyte transport across the porcine distal colon epithelium.
The epithelium from the porcine distal colon was mounted in Ussing chambers and bathed in plasma-like Ringer's solution. Histamine produced increases in current which were not affected by pretreatment with the neural conduction blocker tetrodotoxin. Both the H1-histamine antagonist pyrilamine and the cyclooxygenase inhibitor indomethacin produced dextral shifts in the histamine concentration-response curve. Replacement of Cl with gluconate or HCO3 with tris(hydroxymethyl)aminomethane(tris)-N-2- hydroxyethylpiperazine-N'-2-ethanesulfonic acid in the bathing solution inhibited the mucosal response to histamine by 74 and 23%, respectively. In addition, histamine increased the serosal-to-mucosal Na and Cl fluxes and inhibited the mucosal-to-serosal Na flux, resulting in a reduction of net Na and Cl absorption. Prostaglandin E2 also produced increases in short-circuit current which remained unaffected by tetrodotoxin. Replacement of either Cl or HCO3 inhibited these increases by 85%. Prostaglandin E2 inhibited the mucosal-to-serosal and net Cl fluxes. Leukotriene C4 produced oscillating increases in the short-circuit current which were completely blocked by tetrodotoxin. These increases in current were attributed to an increase in the serosal-to-mucosal Cl flux which resulted in a decrease in net Cl absorption. From these data it was concluded that: 1) histamine interacts with H1-receptors to increase Na and Cl secretion and inhibit Cl absorption; 2) prostaglandin E2 inhibits a HCO3-dependent Cl absorptive pathway, possibly involving Cl/HCO3 exchange and 3) leukotriene C4 acts on enteric nerves to stimulate Cl secretion.
Traynor
T R
TR
Department of Physiology, University of Minnesota, St. Paul 55108.
Brown
D R
DR
O'Grady
S M
SM
D000818:Animals; D012898:Autacoids / Q000494:pharmacology*; D001639:Bicarbonates / Q000493:pharmacokinetics; D001692:Biological Transport / Q000187:drug effects; D002712:Chlorides / Q000493:pharmacokinetics; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D004573:Electrolytes / Q000493:pharmacokinetics*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D013189:SRS-A / Q000494:pharmacology; D012964:Sodium / Q000493:pharmacokinetics; D013552:Swine
D012898:Autacoids; D001639:Bicarbonates; D002712:Chlorides; D004573:Electrolytes; D013189:SRS-A; D006632:Histamine; D012964:Sodium; D015232:Dinoprostone