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ATP Augments Peptide Release from Rat Sensory Neurons in Culture through Activation of P2Y Receptors
ATP has recently emerged as an important proinflammatory mediator that has direct excitatory actions on sensory neurons through activation of ion channel-coupled P2X receptors. The purpose of the current work is to assess whether ATP alters the release of neuropeptides from sensory neurons and the r...
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Published in: | The Journal of pharmacology and experimental therapeutics 2003-09, Vol.306 (3), p.1137-1144 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | ATP has recently emerged as an important proinflammatory mediator that has
direct excitatory actions on sensory neurons through activation of ion
channel-coupled P2X receptors. The purpose of the current work is to assess
whether ATP alters the release of neuropeptides from sensory neurons and the
receptors mediating this putative action. Exposing embryonic sensory neurons
in culture to concentrations of ATP up to 300 μ m did not
increase the release of immunoreactive substance P or calcitonin gene-related
peptide from sensory neurons. However, pre-exposing sensory neurons to 0.1
to100 μ m ATP prior to and throughout administration of 30 nM
capsaicin resulted in a significant augmentation of release evoked by the
vanilloid. This sensitizing action of ATP is blocked by suramin but not
pyridoxal phosphate-6-azobenzene-2,4-disulfonic acid and is mimicked by the
P2Y receptor agonists, 2-2-chloroadenosine triphosphate and UTP, but not by
2-(methylthio)adenosine 5â²-triphosphate or
α,β-methyleneadenosine 5â²-diphosphate. This profile of drug
actions suggests that the sensitizing actions of ATP are mediated by P2Y
receptors. Pretreating sensory neurons with bisindolylmaleimide I, a selective
protein kinase C (PKC) inhibitor, attenuates the augmentation of
capsaicin-induced peptide release by ATP, further implicating P2Y receptors in
the actions of ATP. Immunoblotting also indicates the presence of
P2Y 2 -like immunoreactive substance in embryonic dorsal root ganglia
neurons. Together, these data support the notion that ATP acts at P2Y
receptors in sensory neurons in a PKC-dependent manner to augment their
sensitivity to other stimuli. |
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ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.103.052951 |