TY - JOUR
T1 - Modulation of the nicotinic acetylcholine receptor by dioscorine in clonal rat phaeochlomocytoma (PC12) cells
AU - Nagata, Keiichi
AU - Aistrup, Gary L.
AU - Honda, Hiroshi
AU - Shono, Toshio
AU - Narahashi, Toshio
N1 - Funding Information:
This work was supported by NIH Grant NS14143 and Grant-in-Aid for Developmental Scientific Research 07406003, by Ministry of Education, Science and Culture of Japan 07556014, and by the University of Tsukuba Research Projects. The authors thank Drs. Edson X. Albuquerque and Edna F. R. Pereira of the University of Maryland School of Medicine for providing the PC12 cell line, Nayla Hasan for technical assistance, and Julia Irizarry, Yukiko Sato, and Tokiko Tamaoki for secretarial assistance.
PY - 1999/7
Y1 - 1999/7
N2 - Dioscorine is a toxin isolated from the tubers of tropical yam, Dioscorea hispida Schlussel that has insecticidal and antifeedant activities. The effects of dioscorine on the neuronal nicotinic acetylcholine receptor in rat clonal phaeochlomocytoma (PC12) cells were studied using whole-cell and single-channel patch clamp techniques. Dioscorine at concentrations of 0.45-450 μM accelerated the desensitization of current induced by 100 μM acetylcholine and suppressed the current in a dose-dependent manner. Dioscorine itself did not induce any current at concentrations ranging from 0.45 to 450 μM. At the single-channel level, 4.5-450 μM dioscorine, when co-applied with 10 μM acetylcholine, markedly shortened the open time and caused bursts to appear in a dose-dependent manner. The mean open time, mean closed time, and burst duration were decreased by dioscorine. These changes of single-channel kinetics result in a significant decrease in the total charge carried through the open channels, explaining the suppressive effect of dioscorine on acetylcholine-induced whole-cell currents. The suppressive effect of dioscorine on the acetylcholine-induced current is suggested to play an important role in the toxic actions in animals.
AB - Dioscorine is a toxin isolated from the tubers of tropical yam, Dioscorea hispida Schlussel that has insecticidal and antifeedant activities. The effects of dioscorine on the neuronal nicotinic acetylcholine receptor in rat clonal phaeochlomocytoma (PC12) cells were studied using whole-cell and single-channel patch clamp techniques. Dioscorine at concentrations of 0.45-450 μM accelerated the desensitization of current induced by 100 μM acetylcholine and suppressed the current in a dose-dependent manner. Dioscorine itself did not induce any current at concentrations ranging from 0.45 to 450 μM. At the single-channel level, 4.5-450 μM dioscorine, when co-applied with 10 μM acetylcholine, markedly shortened the open time and caused bursts to appear in a dose-dependent manner. The mean open time, mean closed time, and burst duration were decreased by dioscorine. These changes of single-channel kinetics result in a significant decrease in the total charge carried through the open channels, explaining the suppressive effect of dioscorine on acetylcholine-induced whole-cell currents. The suppressive effect of dioscorine on the acetylcholine-induced current is suggested to play an important role in the toxic actions in animals.
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U2 - 10.1006/pest.1999.2423
DO - 10.1006/pest.1999.2423
M3 - Article
AN - SCOPUS:0032837496
SN - 0048-3575
VL - 64
SP - 157
EP - 165
JO - Pesticide Biochemistry and Physiology
JF - Pesticide Biochemistry and Physiology
IS - 3
ER -