1998 Fiscal Year Final Research Report Summary
Pharmacological studies investigating the mechanisms controlling the peptidergic neurotransmitter release.
| Project/Area Number |
09670093
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
NAKATA Yoshihiro Hiroshima University Faculty of Medicine, TITLE OF POSITION : Professor, 医学部, 教授 (40133152)
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| Project Period (FY) |
1997 – 1998
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| Keywords | substance P / primary afferent neuron / cultured rat spinal dorsal root ganglion cell / substance P release / nerve growth factor / preprotachykinin mRNA / interleukin-1 beta / cyclooxygenase-2 |
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| Research Abstract |
Substance P (SP) in a dorsal root ganglion (DRG) is involved in one of the mechanisms responsible for the transmission of noxious stimuli. To elucidate the mechanisms controlling the release of this peptidergic neurotransmitter, the effects of neurotrophins or interleukin-1beta (IL-1beta) on SP synthesis and release were examined in primary cultured rat DRG cells.
Nerve growth factor (NGF) increased SP content and it's precursor, preprotachykinin (PPT) mRNA in the DRG cells. Another neurotrophins tested, brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) had no effects on the SP content. High concentration of KCl (30mM) or capsaicin evoked the SP release from the cultured rat DRG cells in a Ca^<2+> dependent manner. IL-1beta is one of the cytokines which are synthesized and released from immune cells and considered to be important mediators during inflammation and hyperalgesia. When recombinant mouse IL-1beta was added to the DRG cells in the presence of NGF, IL-1beta evoked the SP release after 3 hours and increased SP content and PPT mRNA after 7 days. The effect of IL-1beta on the SP release was Ca^<2+> dependent and significantly inhibited by a IL-1 receptor antagonist and cyclooxygenase inhibitors, aspirin, indomethacin, NS-398 or dexamethasone. Furthermore IL-1beta increased inducible cyclooxygenase (COX)-2 mRNA without any effects on constitutive COX-1 mRNA in the incubation of 1 hour.
Thus, it is suggested that IL-1beta evoked the release of this nociceptive neuropeptide in the DRG cells via specific IL-1 receptors, the mechanisms of which might be involved in prostanoid systems. It could be responsible for the hyperalgesic action with reference to inflammatory pain in primary afferent neuron to spinal cord pathway.
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