Response to ADP-ribose by activation of TRPM2 in the CRI-G1 insulinoma cell line.
The response to intracellular ADP-ribose in the rat CRI-G1 insulinoma cell line was studied using a patch-clamp method. Dialysis of ADP-ribose into cells induced a response in a dose-dependent manner. The reversal potentials in various solutions showed that the ADP-ribose-gated channel was a Ca2+-permeable nonselective cation channel. In inside-out recordings, ADP-ribose and b-NAD induced responses in the same patch. The single-channel current-voltage relationships for ADP-ribose- and b-NAD-induced responses were almost identical, indicating that ADP-ribose and b-NAD activated the same channel. The physiological properties of the ADP-ribose-gated channel are similar to those we reported previously for the cloned transient receptor potential channel TRPM2. Moreover, RT-PCR analysis showed that TRPM2 was abundantly expressed in CRI-G1 cells, suggesting that the ADP-ribose-gated channel represents the native TRPM2 channel in CRI-G1 cells. These results suggest that ADP-ribose can be an endogenous modulator of Ca2+ influx through the TRPM2 channel into CRI-G1 cells.
Inamura
K
K
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. inamura.kohei@yamanouchi.co.jp
Sano
Y
Y
Mochizuki
S
S
Yokoi
H
H
Miyake
A
A
Nozawa
K
K
Kitada
C
C
Matsushime
H
H
Furuichi
K
K
D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D004305:Dose-Response Relationship, Drug; D007340:Insulinoma / Q000503:physiopathology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels; D008565:Membrane Proteins; D011994:Recombinant Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D007473:Ion Channels; D008565:Membrane Proteins; D011994:Recombinant Proteins; D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D000246:Adenosine Diphosphate Ribose