Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor.
Gymnopilins are substances produced in fruiting bodies of the hallucinogenic mushroom, Gymnopilus junonius. Although, only a few biological effects of gymnopilins on animal tissues have been reported, it is believed that gymnopilins are a key factor of the G. junonius poisoning. In the present study, we found that gymnopilins inhibited ACh-evoked responses in neuronal cell line, PC12 cell, and determine the underlying mechanism. Gymnopilins were purified from wild fruiting bodies of G. junonius collected in Japan. Ca(2+)-imaging revealed that gymnopilins reduced the amplitude of ACh-evoked [Ca(2+)]i rises by about 50% and abolished the ACh responses remaining in the presence of atropine. Gymnopilins greatly reduced the amplitude of [Ca(2+)]i rises evoked by nicotinic ACh receptor agonists, 1,1-Dimethyl-4-phenylpiperazinium iodide (DMPP) and nicotine. In the whole-cell voltage clamp recording, gymnopilins inhibited the DMPP-evoked currents, but did not affect the voltage-gated Ca(2+) channel currents. These results indicate that gymnopilins directly act on nicotinic ACh receptors and inhibit their activity. This biological action of gymnopilins may be one of the causes of the G. junonius poisoning.
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Tomohiko
T
Kayano
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan. Electronic address: nakit@muses.tottori-u.ac.jp.
Naoki
N
Kitamura
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Shunsuke
S
Miyazaki
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Tsuyoshi
T
Ichiyanagi
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Norihiro
N
Shimomura
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Izumi
I
Shibuya
Faculty of Agriculture, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8553, Japan.
Tadanori
T
Aimi
D000109:Acetylcholine / Q000378:metabolism; D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D002118:Calcium; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D006213:Hallucinogens / Q000737:chemistry / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013729:Terpenes / Q000737:chemistry / Q000494:pharmacology*
D006213:Hallucinogens; D011978:Receptors, Nicotinic; D013729:Terpenes; D004246:Dimethylphenylpiperazinium Iodide; D009538:Nicotine; D000109:Acetylcholine; D002118:Calcium
Gymnopilin; Mushroom poisoning; Nicotinic acetylcholine receptor; PC12 cell