1992 Fiscal Year Final Research Report Summary
INHIBITION OF GTP-BINDING PROTEINS BY OPIOIDS
| Project/Area Number |
03670104
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General pharmacology
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| Research Institution | Osaka University |
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Principal Investigator |
SAITO Kihachi OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY, ASSOCIATE PROFESSOR, 歯学部, 助教授 (40110788)
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| Co-Investigator(Kenkyū-buntansha) |
MAEDA Sadaaki OSAKA UNIVERSITY, FACULTY OF DENTISTRY, PHARMACOLOGY, RESEARCH ASSISTANT, 歯学部, 助手 (00135732)
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| Project Period (FY) |
1991 – 1992
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| Keywords | GTP binding proteins / GTP-r-S / DADLE / GDP-GTP exchange reaction |
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| Research Abstract |
Evidence indicates that morphine inhibits neuronal calcium influx through GTP binding proteins and produces an analgesic effect. We previously showed that morphine converts GTP binding proteins to GDP bound form thereby reducing the affinity of calcium antagonist binding. This may result from the inhibition of GDP-GTP exchange reaction or GTPase activity by opioids and be related with the reduction of calcium influx. In the present study, the effect of DADLE on the binding of GTP-r-S was examined.
1) It was observed that treatment of hippocampal slices with 10^<-5>-5x10^<-5>M DADLE followed by the preparation of membrane fractions reduced the binding of ^<35>S-GTP-r-S. There was no change in the affinity of the binding. This decrease of^<35> S-GTP-r-S binding was reversed when 5x10^<-5>M naltrindole was included. The effect was not observed when the membrane fractions were incubated with DADLE.
2) Photaffinity labeling with the use of ^<32>p p3-(4-azidoanilido)-p1 5'-GTP followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis and autoradiography revealed the incorporation of radioactivity into molecular mass of the 43kDa and 33-34kDa proteins. P Photolabeling of both the 43 kDa and 33-34 KDa bands decreased following treatment of hippocampal slices with 10^<-4>M DADLE. These results suggested that DADLE reduces the GDP-GTP exchange in hippocampal membranes.
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