Pharmacological studies investigating the mechanisms controlling the peptidergic neurotransmitter release.

背根神经节（DRG）中的P物质（SP）参与了有害刺激传递的机制之一。为了阐明这种多肽神经递质释放的控制机制，我们在原代培养的大鼠DRG细胞中检测了神经营养因子或白细胞介素-1 β (il -1 β)对SP合成和释放的影响。神经生长因子（NGF）增加了DRG细胞SP及其前体PPT mRNA的含量。另一种神经营养因子，脑源性神经营养因子（BDNF）或神经营养因子-3 （NT-3）对SP含量没有影响。高浓度KCl （30mM）或辣椒素诱导培养的大鼠DRG细胞以Ca^<2+>依赖的方式释放SP。il -1 β是一种由免疫细胞合成并释放的细胞因子，被认为是炎症和痛觉过敏的重要介质。在NGF存在的情况下，将重组小鼠il -1 β加入DRG细胞，il -1 β在3 h后诱导SP释放，7 d后SP含量和PPT mRNA升高。IL-1 β对SP释放的影响是Ca^<2+>依赖的，并被IL-1受体拮抗剂和环氧化酶抑制剂、阿司匹林、吲哚美辛、NS-398或地塞米松显著抑制。il -1 β增加了诱导型环氧合酶(COX)-2 mRNA，但对组成型COX-1 mRNA无影响。因此，这表明IL-1 β通过特异性IL-1受体在DRG细胞中诱发了这种伤害神经肽的释放，其机制可能与前列腺素系统有关。它可能与初级传入神经元到脊髓通路的炎症性疼痛有关。

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.