RT Journal Article
SR Electronic
T1 Troglitazone Inhibits Bicarbonate Secretion in Rat and Human Duodenum
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1080
OP 1084
VO 290
IS 3
A1 M. Hosokawa
A1 H. Tsukada
A1 K. Fukuda
A1 M. Oya
A1 M. Onomura
A1 H. Nakamura
A1 M. Kodama
A1 Y. Yamada
A1 Y. Seino
YR 1999
UL http://jpet.aspetjournals.org/content/290/3/1080.abstract
AB Troglitazone is a new, orally effective antidiabetic agent that decreases plasma glucose in obese patients with non-insulin-dependent diabetes mellitus. Unfortunately, troglitazone also has a propensity to cause edema. This study was designed to determine how troglitazone affects intestinal ion transport and water absorption. Short circuit current (Isc) was measured in rat and human duodenal mucosa in Ussing chambers. Five minutes later, the serosal addition of troglitazone caused Isc to decrease gradually, and after 50 min, Isc reached the peak of decrease. EC50values and maximum response to Isc in rat and human mucosa were 8.4 and 8.7 μM and 8.56 ± 1.0 and 8.00 ± 2.0 μA/cm2, respectively. In an HCO3−/CO2-free system, the decrease in Isc caused by troglitazone was 1.31 ± 0.83 μA/cm2. When 10 mM acetazolamide was preadministered, the small decrease in Isc evoked by troglitazone (20 μM) was 4.56 ± 0.22 μA/cm2, whereas the preadministration of 100 μM amiloride and 100 nM tetrodotoxin did not influence the decrease in Isc evoked by troglitazone. The serosal preadministration of 100 nM vasoactive intestinal peptide potently enhanced the decrease in Iscevoked by 20 μM troglitazone (21.1 ± 1.63 μA/cm2). The cyclic AMP contents of rat duodenal mucosa incubated with and without troglitazone (20 μM) for 50 min were 3.2 ± 0.25 and 5.8 ± 0.46 pmol/mg protein, respectively (P < .01). These results indicate that the ionic basis for the decrease in Isc that is induced by troglitazone may be inhibition of electrogenic bicarbonate secretion. The alteration of intestinal ion transport by troglitazone could cause edema. The American Society for Pharmacology and Experimental Therapeutics