胆碱能信号通路及离子通道介导精氨酸对结肠平滑肌收缩的促进作用  

Cholinergic signaling pathway and ion channels mediate excitatory effect of arginine on colonic muscle contraction of rats

作　　者：全晓静 王晶[1] 谢丹红[1] 范清[1] 王进海[1] QUAN Xiao-jing;WANG Jing;XIE Dan-hong;FAN Qing;WANG Jin-hai(Dept of Gastroenterology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,China)

机构地区：[1]西安交通大学第二附属医院消化内科,陕西西安710004

出　　处：《中国药理学通报》2024年第8期1532-1538,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.82100567);西安交通大学第二附属医院科研基金青年项目[No.YJ(QN)202330]。

摘　　要：目的研究L-精氨酸对大鼠结肠收缩的影响,以阐明其对结肠动力的调节作用和机制。方法采用恒温机槽实验检测结肠平滑肌条自发性收缩活动的变化;采用全细胞膜片钳技术检测L-精氨酸干预前后结肠单个平滑肌细胞电压依赖的L-型钙离子通道(L-type voltage-dependent Ca^(2+)channels,VDCCs)电流和电压依赖钾离子通道(voltage-gated K^(+)channel,Kv)电流的变化。结果L-精氨酸(1 mmol·L^(-1))显著增强结肠纵行平滑肌(P<0.05)和环形平滑肌(P<0.01)自发性收缩活动,且该兴奋作用不被一氧化氮合酶抑制剂Nω-硝基-L-精氨酸(Nω-nitro-L-arginine,L-NNA)(1 mmol·L^(-1))阻断(P>0.05)。而且,河豚毒素(1μmol·L^(-1))和阿托品(1μmol·L^(-1))显著减弱L-精氨酸对结肠平滑肌条收缩的兴奋作用(P<0.05)。此外,L-精氨酸(1 mmol·L^(-1))增加VDCCs峰电流,降低Kv电流(P<0.01)。结论L-精氨酸对大鼠结肠收缩具有促进作用,该作用不依赖内源性NO,可能由碱能信号通路介导。此外,平滑肌细胞VDCCs和Kv通道也参与L-精氨酸对结肠动力的调节。Aim To investigate the effects of L-arginine on spontaneous contraction of rat colon and the relative mechanisms.Methods An organ bath system was use to measure the spontaneous contraction of both longitudinal smooth muscle strips(LMS)and circular muscle strips(CMS).Whole-cell voltage-clamp techniques were applied to observe the alterations in currents of L-type voltage-dependent Ca^(2+)channels(VDCCs),and voltage-gated K^(+)channel(Kv)in single smooth muscle cells(SMCs)from rat colon.Results L-Arginine(1 mmol·L^(-1))significantly enhanced the spontaneous contraction of both LMS and CMS.The excitatory response to L-arginine was remarkably attenuated by tetrodotoxin(1 mmol·L^(-1))and atropine(1 mmol·L^(-1)),antagonist of muscarinic ACh receptor(mAChR).However,the inhibitor of nitric oxide(NO)synthesis L-NNA(1 mmol·L^(-1))failed to block the action of L-Arginine.Furthermore,whole-cell patch-clamp recordings showed that L-arginine activated VDCCs and inhibited Kv channels on SMCs.Conclusions L-Arginine exerts an excitatory effect on colonic motility in a nitric oxide(NO)-independent manner and the stimulatory action of L-arginine is partly mediated by mAChR.In addition,VDCCs and Kv channels are both involved in L-arginine-induced excitation.

关 键 词：L-精氨酸 结肠 平滑肌 离子通道 动力 

分 类 号：R-332[医药卫生] R322.45R322.74R337.2R977.4