Prokineticin 2 suppresses GABA-activated current in rat primary sensory neurons

Prokineticin 2 (PK2) is a newly identified regulatory protein, which is involved in a wide range of physiological processes including pain perception in mammals. However, the precise role of PK2 in nociception is yet not fully understood. Here, we investigate the effects of PK2 on GABAA receptor function in rat trigeminal ganglion neurons using whole-cell patch clamp technique. PK2 reversibly depressed inward currents produced by GABAA receptor activation (IGABA) with an IC50 of 0.26 ± 0.02 nM. PK2 appeared to decrease the efficacy of GABA to GABAA receptor but not the affinity. The maximum response of the GABA dose–response curve decreased to 71.2 ± 7.0% of control after pretreatment with PK2, while the threshold value and EC50 of curve did not alter significantly. The effects of PK2 on IGABA were voltage independent. The PK2-induced inhibition of IGABA was removed by intracellular dialysis of either GDP-β-S (a non-hydrolyzable GDP analog), EGTA (a Ca2+ chelator) or GF109203X (a selective protein kinase C inhibitor), but not by H89 (a protein kinase A inhibitor). These results suggest that PK2 down-regulates the function of the GABAA receptor via G-protein and protein kinase C dependent signal pathways in primary sensory neurons and this depression might underlie the hyperalgesia induced by PK2.