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PMID:15740803

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Citation

Yajima, H, Sato, J, Giron, R, Nakamura, R and Mizumura, K (2005) Inhibitory, facilitatory, and excitatory effects of ATP and purinergic receptor agonists on the activity of rat cutaneous nociceptors in vitro. Neurosci. Res. 51:405-16

Abstract

Pathological pain is often associated with changed sympathetic nerve activities. It is known that sympathetic nerve endings release ATP as a co-transmitter of norepinephrine, but the effect of this ATP on the nociceptive system has not been properly studied in that the concentration range used in the previous studies was much higher than is expected in the surroundings of nociceptor terminals. We examined the effects of ATP, especially at low concentration (10(-5) M or less), on C-fiber polymodal receptor (CPR) activity using a rat skin-nerve preparation in vitro. We found for the first time that ATP inhibited the heat response of CPRs at low concentration (10(-5) M), but facilitated it at high concentration (10(-3) M). The former effect was mimicked by a P2X3 agonist, alpha,beta-methylene ATP, at 10(-5) M, while the latter was mimicked by 2-methylthio ADP (a P2Y1 agonist) or UTP (a P2Y2 agonist) at 10(-3) M, suggesting that the former is mediated by P2X receptors and the latter by P2Y receptors. After repetitive heat stimuli, ATP-induced CPR excitation was increased (10(-5) to 10(-3) M), but none of the purinergic agonists induced CPR excitation in a magnitude comparable to that by ATP. Possible mechanisms for these effects were discussed.

Links

PubMed Online version:10.1016/j.neures.2004.12.008

Keywords

Adenosine Diphosphate/analogs & derivatives; Adenosine Diphosphate/pharmacology; Adenosine Triphosphate/analogs & derivatives; Adenosine Triphosphate/metabolism; Adenosine Triphosphate/pharmacology; Animals; Antineoplastic Agents/pharmacology; Electric Stimulation; Female; Hot Temperature; Nerve Fibers, Unmyelinated/drug effects; Nerve Fibers, Unmyelinated/metabolism; Nociceptors/drug effects; Organ Culture Techniques; Purinergic Agonists; Rats; Rats, Inbred Lew; Skin/innervation; Stimulation, Chemical; Thionucleotides/pharmacology; Uridine Triphosphate/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:P2RY1

involved_in

GO:0019233: sensory perception of pain

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:P2RY2

involved_in

GO:0019233: sensory perception of pain

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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