Trimethyltin chloride induced chloride secretion across rat distal colon.
TMT (trimethyltin chloride), an organotin, is ubiquitous in the environment. The consumption of contaminated food may cause exposure of the human diet to this toxic compound. The present study was to investigate the effects of TMT on the regulation of ion transport across the rat distal colon. The rat colonic mucosa was mounted in Ussing chambers. The effects of TMT were assessed using the Isc (short-circuit current). Both apical and basolateral TMT induced, dose-dependently, an increase in Isc, which was due to a stimulation of Cl- secretion as measured using ion substitution experiments and pharmacological manoeuvres. The secretion was also inhibited by several K+ channel blockers administrated at the basolateral side. When the apical side was permeabilized by nystatin, the TMT-induced K+ conductance was effectively blocked by tetrapentylammonium, a Ca2+-sensitive K+ channel blocker. The response of TMT was sensitive to the basolateral Ca2+ and the intracellular Ca2+ store, which could be disclosed by applying the inhibitors of ryanodine receptors and inositol 1,4,5-trisphosphate receptors. In conclusion, TMT led to Cl- secretion, which was essentially regulated by basolateral Ca2+-sensitive K+ channels. These results suggest the importance of K+ channels in the toxicity hazard of TMT.
Yu
Haijie
H
The School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
Chen
Siliang
S
Yang
Zihuan
Z
Pan
Ao
A
Zhang
Geng
G
Shan
Jiajie
J
Tang
Xiaojiang
X
Zhou
Wenliang
W
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007419:Intestinal Secretions / Q000187:drug effects*; D017136:Ion Transport; D008297:Male; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014298:Trimethyltin Compounds / Q000633:toxicity*
D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D053496:Inositol 1,4,5-Trisphosphate Receptors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D026941:Sodium Channel Blockers; D014298:Trimethyltin Compounds; C040533:trimethyltin chloride