Effect of sodium rhein on electrically-evoked and agonist-induced contractions of the guinea-pig isolated ileal circular muscle

1 This study examined the effects of sodium rhein (0.03-30 mu M) on the contractions of the isolated circular muscle of guinea-pig ileum induced by acetylcholine (100 nM), substance P (3 nM) and electrical stimulation (10 Hz for 0.3 s, 100 mA, 0.5 ms pulse duration). The effect of sodium rhein was also evaluated on the ascending excitatory reflex using a partitioned bath (oral and anal compartments). Ascending excitatory enteric nerve pathways were activated by electrical field stimulation (10 Hz for 2 s, 20 mA, 0.5 pulse duration) in the anal compartment and the resulting contraction of the guinea-pig intestinal circular muscle in the oral compartment was recorded. 2 Sodium rhein (0.3, 3 and 30 mu M) significantly potentiated (52 +/- 11% at 30 mu M) acetylcholine-induced contractions. In the presence of tetrodotoxin (0.6 mu M) or omega-conotoxin GVIA (10 nM) sodium rhein (3 and 30 mu M) did not enhance, but significantly reduced (49 +/- 10% and 44 +/- 8%, respectively, at 30 mu M) acetylcholine-induced contractions. 3 Sodium rhein (0.3, 3 and 30 mu M) significantly increased (65 +/- 11% at 30 mu M) substance P-induced contractions. In the presence of tetrodotoxin (0.6 mu M), omega-conotoxin GVIA (10 nM) or atropine (0.1 mu M), sodium rhein (3 and 30 mu M) significantly reduced (50 +/- 10%, 55 +/- 8% and 46 +/- 10%, respectively, at 30 (mu M) substance P-induced contractions. 4 N-G-nitro-L-arginine methyl ester (L-NAME, 100 mu M) abolished the potentiating effect of sodium rhein on acetylcholine and substance P-induced contractions. At the highest concentration (30 mu M), sodium rhein, in presence of L-NAME, reduced the acetylcholine (30 +/- 6%)- or substance P (36 +/- 6%)induced contractions. 5 Sodium rhein (30 mu M) significantly potentiated (29 +/- 9%) the electrically-evoked contractions. L-NAME (100 mu M), but not phentolamine, enhanced the effect of sodium rhein. Sodium rhein (30 mu M) significantly increased (32 +/- 9%) the ascending excitatory reflex when applied in the oral, but not in the anal compartment. 6 These results indicate that sodium rhein (i) activates excitatory cholinergic nerves on circular smooth muscle presumably through a facilitation of Ca2+ entry through the N-type Ca2+ channel, (ii) has a direct inhibitory effect on circular smooth muscle and (iii) does not affect enteric ascending neuroneural transmission. Nitric oxide could have a modulatory excitatory role on sodium rhein-induced changes of agonist-induced contractions and an inhibitory modulator role on sodium rhein-induced changes of electrically-induced contractions.