ABSTRACT
Aim Tostudytheanalgesiceffectofoxyso-phoridine (OSR)on GABA transporter-1 (GAT-1 )mR-NA expression and its influence on GAT-1 expression inmice.Methods Formalintestwasusedtodetectthe analgesic effect of OSR(iv).Immunohistochemis-try was taken to inspect the expression of GAT-1 in cerebral cortex and thalamus in mouse brain. The quantitative real-time PCR method was used to inspect the influence of OSR on GAT-1 mRNA expression of braininmice.Results OSR(500,250,125mg· kg-1 ,iv ) could significantly increase the foot-licking latency.OSR(500 mg·kg-1,ip)could significantly decrease the number of GAT-1 immuopositive cells incerebral cortex and thalamus in mouse brain,and re-duce GAT-1 mRNA expression in brain(P<0. 01,P<0.05)intheformalintest.Conclusion OSRhasa significant analgesic effect,and its analgesic mecha-nism is related to the GAT-1 expression in mouse brain.
ABSTRACT
<p><b>OBJECTIVE</b>To study the effect of GABA transporter (GAT-1) on the analgesic action of oxysophoridine (OSR) in the central nervous system of mice.</p><p><b>METHOD</b>Hot plate test was used to observe and analyze the effect of gamma aminobutyric acid and the inhibitor of GAT-1 (NO-711) on the analgesic action of oxysophoridine. Real time RT-PCR was used to investigate the influence of OSR on the expression of GAT-1 mRNA induced by formalin in spinal cord and brain of mice.</p><p><b>RESULT</b>Both GABA (2.0 mg x kg(-1), icv) and NO-711(0.125 mg x kg(-1), icv) enhanced the analgesic action of OSR (32.0 mg x kg(-1), iv) in the hot plate test, and the latencies was markedly increased (P < 0.05, P < 0.01). OSR (500.0 mg x kg(-1), iv) significantly inhibited the expression of GAT-1 mRNA induced by formalin (P < 0.05).</p><p><b>CONCLUSION</b>GAT-1 was involved in the analgesia effect of OSR and the down-regulation of GAT-1 mRNA enhanced the analgesic effect.</p>
Subject(s)
Animals , Female , Male , Mice , Alkaloids , Pharmacology , Analgesics , Pharmacology , Brain , Metabolism , Down-Regulation , GABA Plasma Membrane Transport Proteins , Genetics , Metabolism , Gene Expression Regulation , RNA, Messenger , Spinal Cord , MetabolismABSTRACT
.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.
ABSTRACT
Aim To study the analgesic action of oxysophoridine and its effect on the expression of protein kinase C?(PKC?) in dorsal horn of spinal cord(it should be expressed as in dorsal horn of the spinal),cerebral cortex and thalamus of the mice.Methods Hot plate test was used to observe and analyze the analgesic strength and action position of OSR through iv and icv approaches,immunohistochemistry(SABC) was taken to inspect the expression of PKC? in dorsal horn of spinal cord(it should be expressed as in dorsal horn of the spinal),cerebral cortex and thalamus of the mice after administrating OSR.Results The foot-licking latencies of mice were prolonged both iv OSR(500、250、125 mg?kg-1)and icv OSR(100,50,25 mg?kg-1)in the hot plate test(P