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Effect of sodium rhein on electrically‐evoked and agonist‐induced contractions of the guinea‐pig isolated ileal circular muscle
Author(s) -
Izzo Angelo A,
Mascolo Nicola,
Capasso Francesco
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0701900
Subject(s) - tetrodotoxin , acetylcholine , chemistry , atropine , excitatory postsynaptic potential , sodium , stimulation , contraction (grammar) , endocrinology , muscle contraction , medicine , inhibitory postsynaptic potential , biology , organic chemistry
This study examined the effects of sodium rhein (0.03–30 μ M ) on the contractions of the isolated circular muscle of guinea‐pig ileum induced by acetylcholine (100 n M ), substance P (3 n M ) 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. Sodium rhein (0.3, 3 and 30 μ M ) significantly potentiated (52±11% at 30 μ M ) acetylcholine‐induced contractions. In the presence of tetrodotoxin (0.6 μ M ) or ω‐conotoxin GVIA (10 n M ) sodium rhein (3 and 30 μ M ) did not enhance, but significantly reduced (49±10% and 44±8%, respectively, at 30 μ M ) acetylcholine‐induced contractions. Sodium rhein (0.3, 3 and 30 μ M ) significantly increased (65±11% at 30 μ M ) substance P‐induced contractions. In the presence of tetrodotoxin (0.6 μ M ), ω‐conotoxin GVIA (10 n M ) or atropine (0.1 μ M ), sodium rhein (3 and 30 μ M ) significantly reduced (50±10%, 55±8% and 46±10%, respectively, at 30 μ M ) substance P‐induced contractions. N G ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME, 100 μ M ) abolished the potentiating effect of sodium rhein on acetylcholine and substance P‐induced contractions. At the highest concentration (30 μ M ), sodium rhein, in presence of L ‐NAME, reduced the acetylcholine (30±6%)‐ or substance P (36±6%)‐induced contractions. Sodium rhein (30 μ M ) significantly potentiated (29±9%) the electrically‐evoked contractions. L ‐NAME (100 μ M ), but not phentolamine, enhanced the effect of sodium rhein. Sodium rhein (30 μ M ) significantly increased (32±9%) the ascending excitatory reflex when applied in the oral, but not in the anal compartment. These results indicate that sodium rhein (i) activates excitatory cholinergic nerves on circular smooth muscle presumably through a facilitation of Ca 2+ entry through the N‐type Ca 2+ 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.