Project/Area Number |
08457017
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
General physiology
|
Research Institution | Kurume University |
Principal Investigator |
AKASU Takashi Kurume Univ.Sch.Med., Professor, 医学部, 教授 (60113213)
|
Co-Investigator(Kenkyū-buntansha) |
TSURUSAKI Masashi Kurume Univ.Sch.Med., Lecturer, 医学部, 講師 (60207454)
HASUO Hiroshi Kurume Univ.Sch.Med., Associate Prof., 医学部, 助教授 (90172882)
|
Project Period (FY) |
1996 – 1998
|
Project Status |
Completed (Fiscal Year 1998)
|
Budget Amount *help |
¥6,500,000 (Direct Cost: ¥6,500,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥4,000,000 (Direct Cost: ¥4,000,000)
|
Keywords | cytokine / interleukin-1beta / pelvic ganglia / sympathetic ganglia / depolarization / long-lasting hyperpolarization / GABA / presynaptic modulation / 自律神経節 / γ-アミノ酪酸 / パッチクランプ / G-蛋白 / GABA_B受容体 / インターロイキン-1β / 1L-1β活性フラグメント / 骨盤神経叢 / シナプス伝達 / 細胞内シグナル伝達機構 / 大脳中隔核 / 自律神経機能 / ストレス / インターロイキン / 骨盤内神経叢 / 交感神経節 |
Research Abstract |
Interleukin-1 (IL-1) is a cytokine which possesses a wide range of activities in inflammatory, metabolic, haemopoietic and immunological states. Although it is likely that IL-1beta modulates autonomic functions and affect stress processing in various peripheral organs, the effect of IL-1beta on the function of peripheral autonomic neurons is not investigated, in vitro. The aim of the present study was to examine the effect of interleukin-1beta (IL-1beta) on neuronal membrane and synaptic transmission in mammalian pelvic ganglia and bullfrog sympathetic ganglia, in vitro. Bath-application of recombinant human IL-1beta (6 pM-300 nM) for 10 s produced a long-lasting hyperpolarization associated with decreased input resistance in 11 neurons rat major pelvic ganglia (MPG). In other 8 neurons, IL-1beta produced a biphasic response which consists of an initial depolarization followed by a long-lasting hyperpolarization. TTX (3 muM) did not block these responses to IL-1beta. Active fragment of
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IL-1beta (IL-1beta 163-171, 10-100 pM), he active domain of human IL-l(beta, mimicked the effects of IL-1beta. Picrotoxin (100 muM) depressed not only initial depolarization but also hyperpolarization induced by IL-13b (300 nM). These results suggest that yaminobutyric acid (GABA) mediates the biphasic response produced by IL-1beta via GABA_c receptors. Since db-cyclic guanosine monophosphate (GMP) produced an initial depolarization followed by a long-lasting hyperpolarization, cyclic GMP might mediate, at least in part, the IL-1beta-induced hyperpolarization in rat MPG neurons. IL-1beta caused an initial facilitation followed by a long-lasting depression of the EPSP in rabbit vesical pelvic ganglia (VPG) evoked by stimulation of the pelvic nerve. TL-1beta did not affect the depolarizing response produced by acetylcholine (ACh), suggesting that IL-1beta reduces the release of ACh from the pelvic nerve terminals. It is likely that IL-1beta may inhibit the functions of the urinary bladder and other pelvic organs. Less
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