Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X₁ receptor channel currents
- Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X₁ receptor channel currents
- 최선혜; 김현중; 김보라; 신태준; 황성희; 이병환; 이상목; 임혜원; 나승열
- gintonin; LPA receptor; P2X1 receptor; P2X1 receptor potentiation
- Issue Date
- Molecules and cells
- VOL 35, NO 2, 142-150
- Ginseng, the root of Panax ginseng C.A. Meyer, is used as
a general tonic. Recently, we isolated a novel ginsengderived
lysophosphatidic acid (LPA) receptor ligand, gintonin.
Gintonin activates G protein-coupled LPA receptors
with high affinity in cells endogenously expressing LPA
receptors, e.g., Xenopus oocytes. P2X receptors are ligandgated
ion channels activated by extracellular ATP, and 7
receptor subtypes (P2X1-P2X7) have been identified. Most
of the P2X1 receptors are expressed in the smooth muscles
of genitourinary organs involved in reproduction. A
main characteristic of the P2X1 receptor is rapid desensitization
after repeated ATP treatment of cells or tissues expressing
P2X1 receptors. In the present study, we examined
the effect of gintonin on P2X1 receptor channel activity.
P2X1 receptors were heterologously expressed in
Xenopus oocytes. ATP treatment of oocytes expressing
P2X1 receptors induced large inward currents (IATP), but
repetitive ATP treatments induced a rapid desensitization
of IATP. Gintonin treatment after P2X1 receptor desensitization
potentiated IATP in a concentration-dependent manner.
We further examined the signaling transduction pathways
involved in gintonin-mediated potentiation of IATP. Gintonin-
mediated IATP potentiation was blocked by Ki16425,
an LPA1/3 receptor antagonist, a PKC inhibitor, a PLC inhibitor,
and a PI4-Kinase inhibitor but not by a calcium
chelator. In addition, mutations of the phosphoinositide
binding site of the P2X1 receptor greatly attenuated the
gintonin-mediated IATP potentiation. These results indicate
that G protein-coupled LPA receptor activation by gintonin
is coupled to the potentiation of the desensitized P2X1
receptor through a phosphoinositide-dependent pathway.
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