摘要
目的观察各种CBR配体激动剂对急性分离的胰腺腺泡细胞中乙酰胆碱（ACh）诱导的Ca^2＋振荡的影响。方法使用膜片钳全细胞记录，检测大麻素受体1（CB1R）、大麻素受体2（CB2R）和非CBR激动剂对ACh诱发的Ca^2＋振荡的影响。利用野生型（WT）、CB1R敲除（KO）和CB2R-KO小鼠，分别对部分CB2R激动剂和非选择性CBR激动剂（WIN）对小鼠胰腺腺泡细胞Ca^2＋信号的影响进一步检测。结果3种CB2R激动剂均可抑制腺泡细胞内Ca^2＋信号，10 μmol/L的GW，GP1a和JWH133能分别将30 nmol/L ACh引起Ca^2＋振荡的净电流（标准化后）减少至（23.0±4.4）% （P＝0.000，n＝7），（11.0±4.6）% （P＝0.000，n＝6）和（26.0±4.2）% （P＝0.000，n＝9）。而在CB2R-KO小鼠，这三种CB2R激动剂的抑制作用被消除。在WT、CB1R-KO及CB2R-KO小鼠中，非选择性CBR激动剂WIN55，212-2（10 μmol/L）对ACh（30 nmol/L）引起的Ca^2＋振荡的标准化静电流分别减少到（7.0±3.5）% （P＝0.000，n＝6），（5.0±6.9）%（P＝0.000，n＝6）和（5.0±9.3）%（P＝0.000，n＝6）。而内源性大麻样物质2-AG则对Ca^2＋振荡没有影响。结论大麻素受体活性物质调节小鼠的胰腺腺泡细胞中的Ca^2＋信号呈多样性，包括CBR和非CBR，CB2R而不是CB1R在调节小鼠胰腺腺泡细胞中ACh诱导的Ca^2＋振荡起主导作用。
Objective To investigate the effects of various CBR ligands on acetylcholine （Ach） -induced Ca^2＋ oscillations in acute isolated pancreatic acinar cells.Methods Patch-clamp whole-cell recordings were applied to measure ACh-induced intracellular Ca^2＋ oscillations in pancreatic acinar cells acutely dissociated from wild-type （WT）, cannabinoid type 1 receptor （CB1R） knockout （KO）, and cannabinoid type 2 receptor （CB2R） KO mice, and the pharmacological effects of various cannabinoid ligands on the Ca^2＋ oscillations were examined.Results Patch-clamp recordings demonstrated that all tested three CB2R agonists inhibited intracellular Ca^2＋ oscillations, 10 μmol/L of GW, GP1a, and JWH133 can reduced the 30 nmol/L ACh-induced Ca^2＋ oscillations current to （23.0±4.4）% （P=0.000, n=7）, （11.0±4.6）% （P=0.000, n=6） and （26.0±4.2）% （P=0.000, n=9） respectively. In CB2R KO mice, the inhibitory effects of these 3 CB2R agonists were abolished, suggesting that their effect is mediated through the CB2R. In WT, CB1R KO and CB2R KO mice, Non-selective CB receptor agonists WIN55, 212-2 also inhibited Ca^2＋ oscillations, 10 μmol/L of WIN55, 212-2 can reduced the 30 nmol/L ACh-induced Ca^2＋ oscillations current to （7.0±3.5）% （P=0.000, n=6）, （5.0±6.9）% （P=0.000, n=6） and （5.0±9.3）% （P=0.000, n=6） respectively. but endogenous Non-selective cannabinoid substance, 2-AG did not show the inhibitory effect.Conclusion Cannabinoid ligands modulate mouse pancreatic acinar cell Ca^2＋ oscillations in a complex manner, through CB receptors or non-CB receptors. CB2R rather than CB1R plays a critical role in the regulation of Ca^2＋ signals in mouse pancreatic acinar cells.
作者
夏坤锟
郭文治
袁维堂
吴杰
张水军
Xia Kunkun;Guo Wenzhi;Yuan Weitang;Wu Jie;Zhang Shuljun(Department of Colon and Rectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Chin;Henan Key Laboratory of Digestive Organ Transplantation, Open and Key Laboratory of Hepatobiliary ＆ Pa~reatic Surgery and Digestive Organ Transplantation at Henan Univer- sities, Zhengzhou Key Laboratory of Hepatobiliary ＆ Pancreatic Diseases and Organ Transplantation, Zhengzhou 450052, China)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2018年第6期1074-1076,共3页
Chinese Journal of Experimental Surgery
关键词
大麻素受体
钙信号
胰腺腺泡细胞
膜片钳
Cannabinoid receptor
Calcium signals
Pancreatic acinar cells
Patch clamp
作者简介
通信作者：夏坤锟，Email：xkk371885724@126．com
