| Research Abstract |
In this studies, we tried to elucidate functional mechanism f doamine receptors in the striatum from biochemical and pharmacological viewpoints and discuss on mechanisms by which dopaminergic neuronal activtes are regulated. As results, following results were obtained.
By means of slice experiments following Berridge's methds using rat striatum, phospatdyl inositol turnover stimulated by mixed dopamineagnist such as doamine or apomorphine was xamined. As results, increases of PI, P2, P3 reeases were bserved and these increases were dose-dependent.
Inhibiton experiments by use of SCH 23390 or spiperone revealed that this acceeratin of PI turnver was dependent upon doamine D2 receptors.
As next step, cerulein, a CCK 8 analog was ntraperitoneally injected to observe how CCK had effects on dopamine release from rat stratum. For this urpose, in vivo microdialsis experiments were done with the result of increasing effect of CCK on doamine release. In addition, relationship between neuropeptide and dopamine was studied from a viewpoint of immediate early genes. It was noticed that pentylentetrazole indused activation of c-fos was inhiited by bth CCK and neurokinin and such inhibition was antagonized by doamine. Furthermore, we confirmed that these neuropeptide inhibited gene expresion of tyrosine hydroxylase in rat stratum. Emphasis should be put on the fact that there were two hases of crosstalk, i.e. genomic and non-genomic, between sgnal transduction of dopamine and neuropeptides.
|
