In the prairie dog gall bladder set between Ussing chambers, the serosal addition of prostaglandin E2 (PGE2) increased Cl– secretion, while the mucosal addition of PGE2 had almost no effect (Moser et al. 2000). In isolated guinea-pig gallbladder, the serosal addition of PGE2 exerted triphasic influence on the fluid transport, while the mucosal addition of PGE2 induced only small changes in fluid reabsorption (Heintze et al. 1975). Increases of prostaglandins and thromboxane (TX) synthesis were suggested to be associated with an early stage of cholesterol gallstone formation in the prairie dog model (LaMorte et al. 1986).
In this study, we investigated the effects of 9,11-epithio-11,12-methano-TXA2 (STA2), a stable analogue of TXA2, and PGE2 on the short-circuit current (Isc) across the human gall bladder mucosa. The specimens of normal gall bladder mucosa were obtained at cholecystectomy and set between modified Ussing chambers. All procedures are followed by the recommendations of the Declaration of Helsinki. Informed consents were obtained from all patients at Toyama Medical and Pharmaceutical University Hospital. Data are shown as means ± S.E.M. Differences between groups were analysed by one-way ANOVA. Comparison between the two groups was made by paired t test.
The serosal addition of STA2 (0.3 µM) did not significantly affect the Isc (P > 0.05, n = 4). However, the mucosal addition of STA2 (0.3 µM) increased the Isc by 9.7 ± 5.1 µA cm-2 (P < 0.05, n = 4). The mucosal STA2 (0.3 µM) also changed the transepithelial potential difference by -0.4 ± 0.2 mV (lumen negative) and the tissue conductance by 0.54 ± 0.13 mS cm-2 (P < 0.05, n = 4). In RT-PCR experiments, expression of human TXA2 receptor in the gall bladder mucosa was confirmed. Interestingly, the serosal addition of PGE2 (0.5 µM) had no effect (P > 0.05, n = 4), while the mucosal addition of PGE2 increased the Isc by 10.3 ± 6.5 µA cm-2 (P < 0.05, n = 4). These results suggest that TXA2 receptor and prostaglandin EP receptors are present not on the serosal side but on the mucosal side in human gall bladder epithelium.