Tetramethylpyrazine stimulates cystic fibrosis transmembrane conductance regulator-mediated anion secretion in distal colon of rodents

Figure 1 Effect of TMP on ion transport across rat colonic mucosa. A: Representative recordings of I_SC response to TMP (0.1, 1.0, 3.0, and 5.0 mmol/L) added to basolateral side. Arrowheads indicate the time of addition of TMP; B: Concentration-response curve of TMP with response indicated by the total charge transfer per unit area over a 30-min period. Each data point was obtained from at least four individual experiments. Values are mean±SE of maximal increase in I_SC.

Figure 2 Ionic basis of TMP-induced I_SC. A: One millimole per liter of TMP-induced I_SC response (total charge transfer per unit area over 30-min period) obtained in various solutions was plotted with normal KH solution as the control; B: Summarized data showing the effect of 1 mmol/L of TMP-evoked I_SC response in the apical presence of amiloride (0.1 mmol/L), apical Na⁺ removal, and basolateral Na⁺ removal from the bath solution. Values are mean±SE; ^bP < 0.001, ^dP < 0.01 vs control. NS, not significant.

Figure 3 Effect of Cl^- channel blockers. Representative I_SC recording with arrows indicating the response to TMP (5 mmol/L, basolateral) and apical addition of channel blockers DIDS (100 mmol/L) and glibenclamide (1 mmol/L).

Figure 4 Effect of BAPTA-AM on TMP-evoked I_SC. Values are mean±SE; NS, not significant.

Figure 5 Involvement of cAMP in TMP-induced I_SC response. A: Representative recordings of I_SC response to IBM× (100 µmol/L), forskolin (10 µmol/L) without additive effect observed upon subsequent challenge of TMP (1 mmol/L); B: Effect of H₈₉ (5 µmol/L) on TMP (1 mmol/L)-induced I_SC response. Values are mean±SE; ^bP < 0.001 vs control.

Figure 6 Concentration-response curve for TMP-induced transmembrane charges (30 min) in the presence of indomethacin (10 μmol/L). Each data point was obtained from at least four individual experiments. Values are mean±SE of maximal increase in charge.

Figure 7 Effect of TMP on intracellular cAMP level. Each column represents mean±SE; ^aP < 0.05, ^bP < 0.01 vs control (KHS).

Figure 8 A-C: TMP-induced I_SC response in colonic mucosa of mice with CFTR wild-type and homozygous mutation.