Neuropeptide Y inhibits axonal transport of particles in neurites of cultured adult mouse dorsal root ganglion cells.
Neuropeptide Y (NPY) plays a modulatory role in processing nociceptive information. The present study investigated the effects of NPY on axonal transport of particles in neurites of cultured adult dorsal root ganglion (DRG) cells using video-enhanced microscopy. Application of NPY decreased the number of particles transported in both the anterograde and retrograde directions. This effect was persistently observed during NPY application and was reversed after washout. The inhibitory effect of NPY was concentration dependent between 10(-9) M and 10(-6) M. The instantaneous velocity of individual particles moving in anterograde and retrograde directions was also reduced by NPY. Both the NPY Y1 receptor agonist [Leu31,Pro34]-NPY and NPY Y2 receptor agonist NPY(13-36) mimicked the effect of NPY on the number of transported particles. An immunocytochemical study using an antiserum against the NPY Y1 receptor protein revealed that the Y1 receptor was expressed in the majority (85.9 %) of cultured adult mouse DRG cells. Pre-treatment of cells with pertussis toxin, a GTP-binding protein ( G protein) inhibitor, completely blocked the inhibitory effect of NPY. Each application of SQ-22536, an adenylate cyclase inhibitor, and H-89, a protein kinase A inhibitor, mimicked and occluded the effect of NPY. In contrast, dibutyryl cAMP (dbcAMP), a membrane permeable cAMP analogue, and forskolin, an activator of adenylate cyclase, produced a transient increase in axonal transport. The application of dbcAMP and forskolin in combination with NPY negated the effect of NPY alone. These results suggest that NPY, acting at Y1 and Y2 receptors, inhibits axonal transport of particles in sensory neurones. The effect seems to be mediated by a pertussis toxin-sensitive G protein, adenylate cyclase, and protein kinase A pathway. Therefore, NPY may be a modulatory factor for axonal transport in sensory neurones.[1]References
- Neuropeptide Y inhibits axonal transport of particles in neurites of cultured adult mouse dorsal root ganglion cells. Hiruma, H., Saito, A., Kusakabe, T., Takenaka, T., Kawakami, T. J. Physiol. (Lond.) (2002) [Pubmed]
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