title: 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.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Ren
authors.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Qiu
authors.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.
authors.forename: Xiong
authors.initials: X
authors.lastname: Gan
authors.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China.
authors.forename: Zu-Wei
authors.initials: ZW
authors.lastname: Qu
authors.affiliation: Department of Oncology, Wuhan of General Hospital of Guangzhou, People's Liberation Army, 627 Wuluo Road, Wuhan 430070, PR China. Electronic address: raozhiguo@hotmail.com.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Institute of Ion Channels, Department of Pharmacology, Hubei University of Science and Technology, 88 Xianning Road, Xianning 437100, Hubei, PR China. Electronic address: wangping_hu@163.com.
authors.forename: Wang-Ping
authors.initials: WP
authors.lastname: Hu
mesh_terms: D000255:Adenosine Triphosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D004357:Drug Synergism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D058477:Receptors, Purinergic P2X3 / Q000187:drug effects / Q000502:physiology
chemical_list: D005768:Gastrointestinal Hormones; D007211:Indoles; D008301:Maleimides; D009479:Neuropeptides; C486587:Prok2 protein, rat; D058920:Purinergic P2X Receptor Antagonists; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D058477:Receptors, Purinergic P2X3; C513688:prokineticin receptor 2, rat; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; C002630:alpha,beta-methyleneadenosine 5'-triphosphate
keywords: Dorsal root ganglion neuron; Electrophysiology; Mechanical allodynia; Prokineticin 2; α,β-Methylene ATP