Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Eur J Pharmacol. 2011 Aug 1;663(1-3):74-9. doi: 10.1016/j.ejphar.2011.05.002. Epub 2011 May 11.
This study was designed to evaluate the effect of jatrorrhizine on smooth muscle contractions isolated from rat ileum longitudinal muscles. Jatrorrhizine increased the amplitude of spontaneous contractions of ileum longitudinal muscles in concentration-dependent manner with an EC(50) of 30.0±8.4μM. Preincubation of ileum strips with atropine (1μM), 4-diphenyllacetoxy-N (2-chloriethyl)-piperidine (4-DAMP, 1μM) or darifenacin (1μM) significantly inhibited acetylcholine (0.1μM)- and jatrorrhizine (100μM)-induced ileum longitudinal muscle contractions, whereas they were not affected by AF-DX116 (1μM) or hexamethonium (100μM). Pretreatment with SB204070 (1μM) rather than 3-tropanyl-indole-3-carboxyleat (tropisetron, 1μM) significantly inhibited 5-HT (10μM)-induced ileum longitudinal muscle contractions. In contrast, jatrorrhizine-induced ileum longitudinal muscle contractions were not inhibited by tropisetron or SB204070. Furthermore, jatrorrhizine-induced ileum longitudinal muscle contractions were strongly inhibited by nifedipine (1μM), and also attenuated by removal of extracellular Ca(2+), U73122 (1μM), ruthenium red (50μM) or 2-aminoethoxydiphenylborate (2-APB, 10μM). Taken together, jatrorrhizine-elicited spontaneous contractions in rat ileum longitudinal muscles are mediated by activation of acetylcholine receptors, mostly the M(3) receptor. Ca(2+) influx through L-type Ca(2+) channel is significantly contributed to jatrorrhizine-elicited spontaneous contractions, and Ca(2+) release via IP(3) and ryanodine pathways are also involved.
本研究旨在评估黄连碱对大鼠回肠纵行肌平滑肌收缩的影响。黄连碱以浓度依赖的方式增加回肠纵行肌自发性收缩的幅度，其 EC50 为 30.0±8.4μM。用阿托品（1μM）、4-二苯乙酰氧基-N（2-氯乙基）-哌啶（4-DAMP，1μM）或达非那新（1μM）预孵育肠段可显著抑制乙酰胆碱（0.1μM）和黄连碱（100μM）引起的回肠纵行肌收缩，但对 AF-DX116（1μM）或六烃季铵（100μM）无影响。预先用 SB204070（1μM）处理，而非 3-托烷吲哚-3-羧酸酯（曲匹司特，1μM），可显著抑制 5-HT（10μM）引起的回肠纵行肌收缩。相反，黄连碱引起的回肠纵行肌收缩不受曲匹司特或 SB204070 的抑制。此外，黄连碱引起的回肠纵行肌收缩强烈地被硝苯地平（1μM）抑制，并且通过去除细胞外 Ca2+、U73122（1μM）、钌红（50μM）或 2-氨基乙氧基二苯硼酸盐（2-APB，10μM）也可减弱。总之，黄连碱引起的大鼠回肠纵行肌自发性收缩是通过激活乙酰胆碱受体介导的，主要是 M3 受体。通过 L 型钙通道的钙内流对黄连碱引起的自发性收缩有重要贡献，钙释放通过 IP3 和ryanodine 途径也参与。
