大黄酸对豚鼠离体回肠环行肌电刺激诱发收缩和激动剂诱导收缩的影响。

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

作者信息

Izzo A A, Mascolo N, Capasso F

机构信息

Department of Experimental Pharmacology, University of Naples Federico II, Italy.

出版信息

Br J Pharmacol. 1998 Jun;124(4):825-31. doi: 10.1038/sj.bjp.0701900.

DOI:10.1038/sj.bjp.0701900

PMID:9690877

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565453/

Abstract

This study examined the effects of sodium rhein (0.03-30 microM) 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 microM) significantly potentiated (52+/-11% at 30 microM) acetylcholine-induced contractions. In the presence of tetrodotoxin (0.6 microM) or omega-conotoxin GVIA (10 nM) sodium rhein (3 and 30 microM) did not enhance, but significantly reduced (49+/-10% and 44+/-8%, respectively, at 30 microM) acetylcholine-induced contractions. 3. Sodium rhein (0.3, 3 and 30 microM) significantly increased (65+/-11% at 30 microM) substance P-induced contractions. In the presence of tetrodotoxin (0.6 microM), omega-conotoxin GVIA (10 nM) or atropine (0.1 microM), sodium rhein (3 and 30 microM) significantly reduced (50+/-10%, 55+/-8% and 46+/-10%, respectively, at 30 microM) substance P-induced contractions. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) abolished the potentiating effect of sodium rhein on acetylcholine and substance P-induced contractions. At the highest concentration (30 microM), sodium rhein, in presence of L-NAME, reduced the acetylcholine (30+/-6%)- or substance P (36+/-6%)-induced contractions. 5. Sodium rhein (30 microM) significantly potentiated (29+/-9%) the electrically-evoked contractions. L-NAME (100 microM), but not phentolamine, enhanced the effect of sodium rhein. Sodium rhein (30 microM) 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.

摘要

本研究考察了大黄酸（0.03 - 30微摩尔）对由乙酰胆碱（100纳摩尔）、P物质（3纳摩尔）及电刺激（10赫兹，持续0.3秒，100毫安，脉冲持续时间0.5毫秒）诱导的豚鼠回肠离体环行肌收缩的影响。还使用分隔浴槽（口腔和肛门隔室）评估了大黄酸对升支兴奋性反射的作用。通过在肛门隔室施加电场刺激（10赫兹，持续2秒，20毫安，脉冲持续时间0.5毫秒）激活升支兴奋性肠神经通路，并记录口腔隔室中豚鼠肠环行肌由此产生的收缩。2. 大黄酸（0.3、3和30微摩尔）显著增强（30微摩尔时为52±11%）乙酰胆碱诱导的收缩。在存在河豚毒素（0.6微摩尔）或ω-芋螺毒素GVIA（10纳摩尔）的情况下，大黄酸（3和30微摩尔）并未增强，反而显著降低（30微摩尔时分别为49±10%和44±8%）乙酰胆碱诱导的收缩。3. 大黄酸（0.3、3和30微摩尔）显著增加（30微摩尔时为65±11%）P物质诱导的收缩。在存在河豚毒素（0.6微摩尔）、ω-芋螺毒素GVIA（10纳摩尔）或阿托品（0.1微摩尔）的情况下，大黄酸（3和30微摩尔）显著降低（30微摩尔时分别为50±10%、55±8%和46±10%）P物质诱导的收缩。4. NG-硝基-L-精氨酸甲酯（L-NAME，100微摩尔）消除了大黄酸对乙酰胆碱和P物质诱导收缩的增强作用。在最高浓度（30微摩尔）时，在L-NAME存在下，大黄酸降低了乙酰胆碱（30±6%）或P物质（36±6%）诱导的收缩。5. 大黄酸（30微摩尔）显著增强（29±9%）电诱发的收缩。L-NAME（100微摩尔）而非酚妥拉明增强了大黄酸的作用。当在口腔隔室而非肛门隔室应用时，大黄酸（30微摩尔）显著增加（32±9%）升支兴奋性反射。6. 这些结果表明，大黄酸（i）可能通过促进Ca²⁺经N型Ca²⁺通道进入而激活环行平滑肌上的兴奋性胆碱能神经，（ii）对环行平滑肌有直接抑制作用，且（iii）不影响肠升支神经-神经传递。一氧化氮可能对大黄酸诱导的激动剂诱导收缩变化具有调节性兴奋作用，而对大黄酸诱导的电诱导收缩变化具有抑制性调节作用。