Short-chain fatty acids have polarized effects on sodium transport and intracellular pH in rabbit proximal colon  Joseph H. Sellin, Roland De Soignie  Gastroenterology  Volume 114, Issue 4, Pages 737-747 (April 1998) DOI: 10.1016/S0016-5085(98)70587-6 Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 1 Effects of unilateral propionate on pHi. Propionate (20 mmol/L) was added to either the (A) mucosal or (B) serosal reservoir of a specifically designed fluorospectrometric cuvette, as described in Materials and Methods. pHi was determined by BCECF. Both mucosal and serosal propionate caused a rapid decrease in pHi, but the recovery was slower and less marked after serosal SCFA. Note the difference in scale. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 1 Effects of unilateral propionate on pHi. Propionate (20 mmol/L) was added to either the (A) mucosal or (B) serosal reservoir of a specifically designed fluorospectrometric cuvette, as described in Materials and Methods. pHi was determined by BCECF. Both mucosal and serosal propionate caused a rapid decrease in pHi, but the recovery was slower and less marked after serosal SCFA. Note the difference in scale. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 2 Amiloride effects the pHi recovery. Mucosal amiloride (10−3 mmol/L; (▨) significantly inhibited the pHi recovery after addition of 20 mmol/L propionate to the mucosal surface. In contrast, serosal amiloride (□) did not impede the pHi recovery after mucosal propionate. In these studies, amiloride was added selectively to either the mucosal or serosal reservoir, a new baseline was established, and then propionate was added. The differential response suggests that apical NHE may be a more critical homeostatic mechanism in SCFA-induced pHi changes. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 3 Effect of propionate gradients on Na+ transport. Unidirectional and net Na+ fluxes were determined in the presence of either a physiologically directed propionate gradient (□, n = 30), bilaterally equal SCFAs (▨, n = 4), or a serosa-to-mucosa gradient (■, n = 6). Na+ absorption was significantly altered by SCFA gradients without a corresponding change in Isc. *P < 0.05 vs. 50/50 propionate. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 4 Effect of lactate on Na+ transport. Unidirectional and JNanet were determined in the presence of either a mucosa-to-serosa lactate gradient (■) or equimolar bilateral lactate (□). The gradient conditions were associated with a significant increase in both JNams and JNanet. P < 0.05 vs. controls. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 5 Additive stimulation of Na+ absorption by epinephrine. Sequential flux studies measured Na+ absorption under control conditions, with a 50/0 mucosa-to-serosa propionate gradient (□, control), and after the addition of 50 μmol/L epinephrine serosally (■). Despite the increased Na+ absorption under gradient conditions, epinephrine induced significant increases in JNams and JNanet . P < 0.05 vs. controls. The increase in JNanet, 4.25 μEq · cm−2 · h−1, is similar to the effects of epinephrine in the absence of a gradient11 (n = 22). Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 6 Effect of buffers on propionate-stimulated Na+ absorption. Na+ fluxes were measured under 50/0 mucosa-to-serosa propionate gradient conditions either with a HEPES or bicarbonate buffer (control conditions [□]). The stimulation of Na+ absorption by epinephrine was determined in a subsequent flux period (■); unlike the effect of buffers on gradient-stimulated Na+ absorption, epinephrine's effect was not altered by changing from HEPES to bicarbonate buffers (n = 5 for each group). Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 7 Inhibition of SCFA gradient–stimulated Na+ absorption. Na+ fluxes were measured with a 50/0 mucosa-to-serosa gradient in a HEPES-buffered solution (control, n = 22). Gluconate substitution for chloride (n = 8) and 2 mmol/L DIDS (n = 7) mucosally both significantly inhibited net Na+ absorption. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 8 Effect of transport inhibitors on SCFA gradient–stimulated Na+ absorption. Na+ absorption was determined in the presence of a 50/0 mucosa-to-serosa propionate gradient (control). A series of recognized transport inhibitors including 2 mmol/L serosal DIDS, 1 mmol/L mucosal amiloride, 0.1 mmol/L mucosal EIPA, and bilateral 8-bromo-cAMP and cinnamate were added in five sets of tissue. None of these agents had a significant inhibitory effect on Na+ transport. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions

Fig. 9 Effect of transport inhibitors on epinephrine-stimulated Na+ absorption. Flux studies were performed in the presence of a 50/0 mucosa-to-serosa propionate gradient and a series of transport inhibitors. After a baseline flux was determined (Figures 7 and 8), 5.5 μmol/L epinephrine was added serosally and a second flux period was measured. ΔJNanet represents the change induced by epinephrine in the presence of inhibitors. The number of experiments for each inhibitor is the same as in Figure 8. Gastroenterology 1998 114, 737-747DOI: (10.1016/S0016-5085(98)70587-6) Copyright © 1998 American Gastroenterological Association Terms and Conditions