Prokineticin 2 facilitates mechanical allodynia induced by α,β-methylene ATP in rats.

Abstract

Prokineticin 2 (PK2), a new chemokine, causes mechanical hypersensitivity in the rat hind paw, but little is known about the molecular mechanism. Here, we have found that ionotropic P2X receptor is essential to mechanical allodynia induced by PK2. First, intraplantar injection of high dose (3 or 10 pmol) of PK2 significantly increased paw withdrawal response frequency (%) to innocuous mechanical stimuli (mechanical allodynia). And the mechanical allodynia induced by PK2 was prevented by co-administration of TNP-ATP, a selective P2X receptor antagonist. Second, although low dose (0.3 or 1 pmol) of PK2 itself did not produce an allodynic response, it significantly facilitated the mechanical allodynia evoked by intraplantar injection of α,β-methylene ATP (α,β-meATP). Third, PK2 concentration-dependently potentiated α,β-meATP-activated currents in rat dorsal root ganglion (DRG) neurons. Finally, PK2 receptors and intracellular signal transduction were involved in PK2 potentiation of α,β-meATP-induced mechanical allodynia and α,β-meATP-activated currents, since the potentiation were blocked by PK2 receptor antagonist PKRA and selective PKC inhibitor GF 109203X. These results suggested that PK2 facilitated mechanical allodynia induced by α,β-meATP through a mechanism involved in sensitization of cutaneous P2X receptors expressed by nociceptive nerve endings.

• Authors: Cuixia Ren, Chun-Yu Qiu, Xiong Gan, Ting-Ting Liu, Zu-Wei Qu, Zhiguo Rao, Wang-Ping Hu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 767 Pg. 24-9 (Nov 15 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26435025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Gastrointestinal Hormones
• Indoles
• Maleimides
• Neuropeptides
• Prok2 protein, rat
• Purinergic P2X Receptor Antagonists
• Receptors, G-Protein-Coupled
• Receptors, Peptide
• Receptors, Purinergic P2X3
• prokineticin receptor 2, rat
• 2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate
• Adenosine Triphosphate
• Protein Kinase C
• bisindolylmaleimide I
• alpha,beta-methyleneadenosine 5'-triphosphate

Topics

• Adenosine Triphosphate (adverse effects, analogs & derivatives, pharmacology)
• Animals
• Drug Synergism
• Ganglia, Spinal (drug effects, physiology)
• Gastrointestinal Hormones (antagonists & inhibitors, pharmacology)
• Hyperalgesia (chemically induced, physiopathology)
• Indoles (pharmacology)
• Male
• Maleimides (pharmacology)
• Membrane Potentials (drug effects, physiology)
• Neuropeptides (antagonists & inhibitors, pharmacology)
• Protein Kinase C (antagonists & inhibitors)
• Purinergic P2X Receptor Antagonists (pharmacology)
• Rats
• Receptors, G-Protein-Coupled (antagonists & inhibitors)
• Receptors, Peptide (antagonists & inhibitors)
• Receptors, Purinergic P2X3 (drug effects, physiology)