Bauer M B, Murphy S, Gebhart G F
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242, USA.
J Neurochem. 1995 Jul;65(1):363-72. doi: 10.1046/j.1471-4159.1995.65010363.x.
Capsaicin stimulates cyclic GMP production via nitric oxide (NO) (or another nitrosyl factor) in dorsal root ganglion (DRG) neurons maintained in culture. The purpose of the present study was to characterize further capsaicin stimulation of cyclic GMP production in DRG cells maintained in culture, investigate other algesic and/or inflammatory agents for effects on cyclic GMP production, and examine cells responsible for NO production and cyclic GMP production. Capsaicin stimulation of cyclic GMP production in DRG cells was dose dependent, receptor mediated, and attenuated by hemoglobin. Prostaglandin E2, substance P, and calcitonin gene-related peptide did not affect basal, capsaicin-stimulated, or bradykinin-stimulated cyclic GMP production. Other inflammatory or algesic agents, including serotonin, histamine, ATP, glutamate, aspartate, and NMDA, did not affect cyclic GMP production. Pretreatment of DRG cells with lipopolysaccharide increased basal cyclic GMP production in neuronal but not in nonneuronal cultures and facilitated stimulation of cyclic GMP production by L-arginine. Capsaicin pretreatment of neuronal DRG cultures, which destroys capsaicin-sensitive (small diameter) afferent neurons, attenuated capsaicin- and bradykinin-stimulated cyclic GMP production but did not affect basal or sodium nitroprusside-stimulated cyclic GMP production. These results indicate that capsaicin elicits production of a nitrosyl factor via capsaicin-sensitive (small diameter) neurons. Capsaicin evoked cyclic GMP production in nonneuronal DRG cultures in the presence but not in the absence of apposed neuronal DRG cultures. Overall, these findings suggest that specific exogenous (or endogenous) substances may stimulate production of a nitrosyl factor(s) by a subset of DRG neurons, and nitrosyl factors produced by these neurons may affect cyclic GMP production in neighboring neuronal or non-neuronal cells.
辣椒素通过一氧化氮（NO）（或另一种亚硝酰基因子）刺激培养的背根神经节（DRG）神经元中的环磷酸鸟苷（cGMP）生成。本研究的目的是进一步表征辣椒素对培养的DRG细胞中环磷酸鸟苷生成的刺激作用，研究其他致痛和/或炎症介质对环磷酸鸟苷生成的影响，并检查负责一氧化氮生成和环磷酸鸟苷生成的细胞。辣椒素对DRG细胞中环磷酸鸟苷生成的刺激作用呈剂量依赖性、受体介导性，并可被血红蛋白减弱。前列腺素E2、P物质和降钙素基因相关肽不影响基础、辣椒素刺激或缓激肽刺激的环磷酸鸟苷生成。其他炎症或致痛介质，包括5-羟色胺、组胺、三磷酸腺苷、谷氨酸、天冬氨酸和N-甲基-D-天冬氨酸，不影响环磷酸鸟苷生成。用脂多糖预处理DRG细胞可增加神经元培养物而非非神经元培养物中的基础环磷酸鸟苷生成，并促进L-精氨酸对环磷酸鸟苷生成的刺激作用。对神经元DRG培养物进行辣椒素预处理可破坏对辣椒素敏感（小直径）的传入神经元，减弱辣椒素和缓激肽刺激的环磷酸鸟苷生成，但不影响基础或硝普钠刺激的环磷酸鸟苷生成。这些结果表明，辣椒素通过对辣椒素敏感（小直径）的神经元引发亚硝酰基因子的生成。在存在而非不存在并置的神经元DRG培养物的情况下，辣椒素可在非神经元DRG培养物中诱发环磷酸鸟苷生成。总体而言，这些发现表明特定的外源性（或内源性）物质可能刺激DRG神经元亚群产生亚硝酰基因子，而这些神经元产生的亚硝酰基因子可能影响邻近神经元或非神经元细胞中的环磷酸鸟苷生成。
