Mechanisms of bupivacaine inhibition of glutamate-induced intracellular calcium elevation in primary cultured rat hippocampal astrocytes
10.16438/j.0513-4870.2020-0842
- VernacularTitle:布比卡因抑制谷氨酸诱导大鼠海马星形胶质细胞内钙升高的机制
- Author:
Huan-huan MA
1
;
Xiao-que ZHU
1
;
Wen-yan GUO
1
;
Jie HAO
1
;
Bao-hua JIN
1
;
Wei ZHANG
1
Author Information
1. Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang 050017, China
- Publication Type:Research Article
- Keywords:
bupivacaine;
mGluR5 receptor;
glutamate;
astrocyte
- From:
Acta Pharmaceutica Sinica
2020;55(7):1614-1621
- CountryChina
- Language:Chinese
-
Abstract:
This research investigated the mechanism by which bupivacaine inhibits glutamate-induced intracellular free Ca2+ increases in primary cultured hippocampal astrocytes. Immunofluorescence was used to demonstrate the expression of metabotropic glutamate receptor (mGluR5 receptor) on neurons and astrocytes. Calcium imaging was used to measure the alteration of intracellular free Ca2+ ([Ca2+]i) in primary cultured rat hippocampal neurons and astrocytes. The animal experiments were approved by the Animal Experiments Ethical Committee of Hebei Medical University. The results showed that mGluR5 receptor was abundantly expressed in the primary cultured rat neurons and astrocytes. Bupivacaine (300 μmol·L-1) significantly inhibited 1 mmol·L-1 glutamate-induced [Ca2+]i increase in astrocytes (P < 0.01). 2-Methyl-6-(2-phenylethynyl)-pyridine (MPEP) (10 μmol·L-1) completely abolished the increase of [Ca2+]i induced by 1 mmol·L-1 glutamate in the astrocytes (P < 0.01), while the inhibitory effect on neurons was only 10%-20%. Bupivacaine (300 μmol·L-1) completely inhibited the [Ca2+]i increase induced by mGluR5 receptor agonists (RS)-3,5-dihydroxyphenylglycine (DHPG) (50 μmol·L-1) and (RS)-2-chloro-5-hydroxyphenylglycine sodium salt (CHPG) (1 mmol·L-1) in astrocytes (P < 0.01). In addition, bupivacaine inhibited the CHPG-induced [Ca2+]i increase in a dose-dependent manner in astrocytes with an IC50 of 100 μmol·L-1. The results from this study indicate that bupivacaine inhibits glutamate-induced [Ca2+]i elevation by acting on the mGluR5 receptor in primary cultured hippocampal astrocytes.
