Molecular biological and pharmacological study on the roles of brain interleukin-1 in transmission and regulation of nociceptive information
| Project/Area Number |
05454569
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
|
|---|
| Research Institution | KYOTO UNIVERSITY |
|---|
Principal Investigator |
SATOH Masamichi Kyoto University, Faculty of Pharmaceutical Sciences, Professor, 薬学部, 教授 (80025709)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MINAMI Masabumi Kyoto University, Faculty of Pharmaceutical Sciences, Instructor, 薬学部, 助手 (20243040)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥5,700,000 (Direct Cost: ¥5,700,000)
|
|---|
| Keywords | Interleukin-1beta / Interleukin-1 Receptor / Cytokine / Hyperalgesia / Analgesia / Adrenergic / インターロイキン-1β変換酵素 |
|---|
| Research Abstract |
In this study, we conducted the following expeiments to elucidate the roles of brain interleukin-1beta in the modulation of nociceptive information. First, IL-1beta was intracerebroventriculary administrated and the nociceptive threshold to mechanical stimulation was measured. The lower doses (10,000 pg) of IL-1beta induced hyperalgesia, but the higher doses (1,10 ng) of IL-1beta induced analgesia. These effects of IL-1beta on the nociceptive threshold were inhibited by the simultaneous administration of IL-1 receptor antagonist.
Hyperalgesia induced by the lower dose of IL-1beta but not analgesic effects by the higher dose of IL-1beta, was suppressed by pretreatment of sodium salicylate. Pretreatment of alpha-helical-CRF inhibited both hyperalgesic and analgesic effects of IL-1beta. Secondly, we examined the distribution of IL-1 receptor mRNA in the rat brain using in situ hybridization technique. Type I IL-1 receptor mRNA was observed in the several nuclei of the thalamus, amygdala and medulla. In these nuclei type I IL-1 receptor mRNA was localized on the neuronal cells which express neuron specific enolase mRNA.Type II IL-1 receptor mRNA was not observed in the normal rat brain. As regard for IL-1beta converting enzyme , a key enzyme for processing the IL-1beta precursor protein to produce mature IL-1beta, its mRNA was not detected in the normal rat brain. Furthermore, an administration of isoproterenol, which had been shown to induce IL-1beta mRNA in the rat hypothalamus, caused significant expression of IL-1beta mRNA at 1 hr after administration in several brain regions. In addition, analgesic effects of isoproterenol were observed. Lastly, increased expression of IL-1beta mRNA was observed in the hypothalamus after i.p.l.administration of formalin, which induced sustained pain. These data strongly suggest that IL-1beta is involved in the regulation of nociceptive information in the brain.
|
Report
(3 results)
Research Products
(10 results)
