作者：Meng; LIU; Yi; YANG; Bo; TAN; Yu-lei; ...
摘要：OBJECTIVE To explore the mechanism of Gαi and Gβγ subunits on dexmedetomidine（DMED）-induced sedation.METHODS Kunming mice were randomly placed into three groups（DMED group,DMED+dbcAMP/rolipram/gallein/M119 group,dbcAMP/rolipram/gallein/M119 group） to explore the regulation of dbcAMP/rolipram/gallein/M119 on DMED-induced sedation by establishing loss of righting reflex（LORR） model.DbcAMP/rolipram was intracerebroventricular injected and gallein/M119 was intraperitoneal injected 15 min before DMED intravenous injection.In CHO-α2 A-AR cells,after administration of DMED/gallein/M119,the regulation on the cAMP accumulation stimulated by Forskolin（FSK） was detected,so was the intracellular calcium ion concentration([Ca2 + ]i.The levels of pERK/pCREB were detected by Western Blot to explore the key signal molecules involved in DMED-induced sedation.RESULTS The ED50 of DMED-induced LORR(200.0 nmol·kg-1) was increased to 375.0 or433.3 nmol·kg-1 by pre-treatment with cAMP analog dbcAMP（50 nmol/5μl per mouse） or phosphodies.terase 4 inhibitor rolipram（100 nmol/5μl per mouse）.In addition,the ED50 of DMED-induced LORR was decreased to 113.6 or 136.5 nmol·kg-1 when pre-treated with Gβγ subunits inhibitor M119(100 mg·kg-1)or gallein(100 mg·kg-1) respectively.Administration of dbcAMP,rolipram,gallein or M119 alone had little effect on LORR of mice.Gallein(10 μmol·L-1) significantly inhibited forskolin-stimulated cAMP accumu.lation in CHO-α2A-AR cells.Compared with Gβγ subunits inhibitors or DMED alone,[Ca2+]i and pERK1/2 significantly increased after co-administration of Gβγ subunits inhibitors with DMED.DbcAMP(5 μmol·L-1)or rolipram(5 μmol·L-1) alone had little effect on ERK1/2 phosphorylation,but decreased DMEDinduced ERK1/2 phosphorylation after co-administration with DMED.Gβγ subunit inhibitors treatment increased DMED-induced phosphorylation of CREB,whereas dbcAMP or rolipram had little effect on pCREB induced by DMED.CONCLUSION Gβγ subunits might inhibit DMED-induced seda
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