title: Prolactin potentiates the activity of acid-sensing ion channels in female rat primary sensory neurons.
abstract: Prolactin (PRL) is a polypeptide hormone produced and released from the pituitary and extrapituitary tissues. It regulates activity of nociceptors and causes hyperalgesia in pain conditions, but little is known the molecular mechanism. We report here that PRL can exert a potentiating effect on the functional activity of acid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRL dose-dependently increased the amplitude of ASIC currents with an EC50 of (5.89 ± 0.28) × 10(-8) M. PRL potentiation of ASIC currents was also pH dependent. Second, PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRL receptor antagonist, and removed by intracellular dialysis of either protein kinase C inhibitor GF109203X, protein interacting with C-kinase 1(PICK1) inhibitor FSC-231, or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membrane excitability of DRG neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acid stimuli. Four, PRL exacerbated nociceptive responses to injection of acetic acid in female rats. Finally, PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behavior in intact female rats than OVX female and male rats and thus modulation of PRL may be gender-dependent. These results suggest that PRL up-regulates the activity of ASICs and enhances ASIC mediated nociceptive responses in female rats, which reveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia.
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: 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: 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. Electronic address: qiuchunyu1225@126.com.
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. Electronic address: wangping_hu@163.com.
authors.forename: Wang-Ping
authors.initials: WP
authors.lastname: Hu
mesh_terms: D019342:Acetic Acid / Q000494:pharmacology; D062565:Acid Sensing Ion Channels / Q000502:physiology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D059225:Nociception / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D011522:Protons; D051381:Rats; D017207:Rats, Sprague-Dawley; D011981:Receptors, Prolactin / Q000037:antagonists & inhibitors / Q000502:physiology; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D062565:Acid Sensing Ion Channels; D011522:Protons; D011981:Receptors, Prolactin; C506484:prolactin, delta(1-9)-Arg(129)-; D011388:Prolactin; D019342:Acetic Acid
keywords: Acid-sensing ion channel; Dorsal root ganglion neuron; Electrophysiology; Nociceptive behavior; Prolactin