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Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.

ABSTRACT: 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 microM) 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 microM) and suramin (100 microM) 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.

SUBMITTER: Kanekar S

PROVIDER: S-EPMC3097387 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.

Kanekar Shami S Jia Cuihong C Hegg Colleen Cosgrove CC

Journal of neuroscience research 20090501 6

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 neurope ...[more]

PMID: 19115410

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Project description:Adenosine triphosphate (ATP) is released from cholangiocytes into bile and is a potent secretogogue by increasing intracellular Ca²(+) and stimulating fluid and electrolyte secretion via binding purinergic (P2) receptors on the apical membrane. Although morphological differences exist between small and large cholangiocytes (lining small and large bile ducts, respectively), the role of P2 signaling has not been previously evaluated along the intrahepatic biliary epithelium. The aim of these studies therefore was to characterize ATP release and P2-signaling pathways in small (MSC) and large (MLC) mouse cholangiocytes. The findings reveal that both MSCs and MLCs express P2 receptors, including P2X4 and P2Y2. Exposure to extracellular nucleotides (ATP, uridine triphosphate, or 2',3'-O-[4-benzoyl-benzoyl]-ATP) caused a rapid increase in intracellular Ca²(+) concentration and in transepithelial secretion (I(sc)) in both cell types, which was inhibited by the Cl(-) channel blockers 5-nitro-2-(-3-phenylpropylamino)-benzoic acid (NPPB) or niflumic acid. In response to mechanical stimulation (flow/shear or cell swelling secondary to hypotonic exposure), both MSCs and MLCs exhibited a significant increase in the rate of exocytosis, which was paralleled by an increase in ATP release. Mechanosensitive ATP release was two-fold greater in MSCs compared to MLCs. ATP release was significantly inhibited by disruption of vesicular trafficking by monensin in both cell types.These findings suggest the existence of a P2 signaling axis along intrahepatic biliary ducts with the "upstream" MSCs releasing ATP, which can serve as a paracrine signaling molecule to "downstream" MLCs stimulating Ca²(+)-dependent secretion. Additionally, in MSCs, which do not express the cystic fibrosis transmembrane conductance regulator, Ca²(+)-activated Cl(-) efflux in response to extracellular nucleotides represents the first secretory pathway clearly identified in these cholangiocytes derived from the small intrahepatic ducts.

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Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.

Publications

Purinergic receptor activation evokes neurotrophic factor neuropeptide Y release from neonatal mouse olfactory epithelial slices.

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