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Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices
Author(s) -
Kanekar Shami,
Jia Cuihong,
Hegg Colleen Cosgrove
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21954
Subject(s) - olfactory epithelium , ppads , purinergic receptor , p2 receptor , neuropeptide y receptor , purinergic signalling , endocrinology , medicine , biology , olfactory mucosa , olfactory system , neurotrophic factors , olfactory ensheathing glia , olfactory nerve , receptor , microbiology and biotechnology , chemistry , neuropeptide , neuroscience , central nervous system , olfactory bulb , adenosine , adenosine receptor , agonist
One premise regarding the mechanism of injury‐evoked neuroregeneration is that injured cells induce the release of neurotrophic factors to trigger neurogenesis. Extracellular purine nucleotides exert multiple neurotrophic actions in the central nervous system mediated via activation of purinergic receptors. However, whether purinergics have a neurotrophic role in the olfactory neuroepithelium has not been investigated. Thus, we monitored the ATP‐induced release of neuropeptide Y (NPY), a neuropeptide that increases neuroproliferation in the olfactory epithelium. To visualize NPY release, slices of olfactory epithelium from neonatal mice were cultured on nitrocellulose paper. Immunoassays of the nitrocellulose demonstrated NPY immunoreactivity in regions corresponding to the olfactory epithelium of the nasal cavity. One hour of exposure to exogenous ATP (100, 500 μM) significantly increased the number of olfactory epithelium slices that released NPY from 25% ± 6% to 60% ± 7% or 71% ± 10% ( P = 0.001). The purinergic receptor antagonists pyridoxalphosphate‐6‐azophenyl‐2′,4′‐disulfonic acid (PPADS; 25 μM) and suramin (100 μM) significantly reduced the number of olfactory epithelium slices exhibiting ATP‐evoked NPY release to 18% ± 11% ( P = 0.004), indicating that NPY release is mediated by activation of purinergic receptors. Released NPY was quantified by enzyme and radioimmunoassays. Exogenous ATP or UTP significantly increased the amount of NPY released. Overall, this study demonstrates that purinergic receptor activation mediates the release of neurotrophic factor NPY in the olfactory epithelium and provides pharmacological targets to promote regeneration of damaged olfactory epithelium. © 2008 Wiley‐Liss, Inc.