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 GABA(A) receptor function in rat trigeminal ganglion neurons using whole-cell patch clamp technique. PK2 reversibly depressed inward currents produced by GABA(A) receptor activation (I(GABA)) with an IC₅₀ of 0.26 ± 0.02 nM. PK2 appeared to decrease the efficacy of GABA to GABA(A) 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 I(GABA) were voltage independent. The PK2-induced inhibition of I(GABA) 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 GABA(A) 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.
Xiong
Yan-Cai
YC
Department of Pharmacology, Xianning College, 88 Xianning Road, Xianning 437100, Hubei, PR China.
Li
Xue-Mei
XM
Wang
Xue-Jing
XJ
Liu
Yu-Qiang
YQ
Qiu
Fang
F
Wu
Dan
D
Gan
Yun-Bo
YB
Wang
Bang-Hua
BH
Hu
Wang-Ping
WP
D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D005768:Gastrointestinal Hormones / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D011984:Sensory Receptor Cells / Q000502:physiology*; D015398:Signal Transduction; D012668:Trigeminal Ganglion / Q000166:cytology / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D005768:Gastrointestinal Hormones; D009479:Neuropeptides; D011963:Receptors, GABA-A; C513686:prokineticin 2, rat; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins