Enhancement Of Prolactin On Activity Of Acid Sensitive Ion Channels In Primary Sensory Neurons Of Female Rats

Prolactin (PRL) is a polypeptide hormone produced and released from thepituitary and extrapituitary tissues. It regulates activity of nociceptors and causeshyperalgesia in pain conditions, but little is known the molecular mechanism. Wereport here that PRL can exert a potentiating effect on the functional activity ofacid-sensing ion channels (ASICs), key sensors for extracellular protons. First, PRLdose-dependently increased the amplitude of ASIC currents with an EC50of (5.89±0.28)×10-8M. PRL potentiation of ASIC currents was also pH dependent. Second,PRL potentiation of ASIC currents was blocked by Δ1-9-G129R-hPRL, a PRLreceptor antagonist, and removed by intracellular dialysis of either protein kinase Cinhibitor GF109203X, protein interacting with C-kinase1(PICK1) inhibitor FSC-231,or PI3K inhibitor AS605240. Third, PRL altered acidosis-evoked membraneexcitability of DRG neurons and caused a significant increase in the amplitude of thedepolarization and the number of spikes induced by acid stimuli. Four, PRLexacerbated nociceptive responses to injection of acetic acid in female rats. Finally,PRL displayed a stronger effect on ASIC mediated-currents and nociceptive behaviorin intact female rats than OVX female and male rats and thus modulation of PRL maybe gender-dependent. These results suggest that PRL up-regulates the activity ofASICs and enhances ASIC mediated nociceptive responses in female rats, whichreveal a novel peripheral mechanism underlying PRL involvement in hyperalgesia.