Abstract:Gymnopilus junonius is a widely spread mushroom in Japan and well known as a hallucinogenic mushroom. Gymnopilin was purified from the fruiting body of G. junonius and was reported to act on the spinal cord and depolarize motoneurons. This is the only evidence that gymnopilin has a biological effect on animals and no mechanism of the action has been determined at all. In this study, we examined effects of gymnopilin on intracellular Ca . These results indicate that gymnopilin activated phospholipase C and mobi… Show more
“…We have recently reported that gymnopilins activate two intracellular signal cascades including the phospholipase C-dependent one (Miyazaki et al, 2012) and the cAMP-dependent one (Nishio et al, 2012). In addition, here we report that gymnopilins act on the nAChR.…”
Section: Junoniussupporting
confidence: 65%
“…Gymnopilins were purified from the wild fruiting body of G. junonius collected in Japan according to the procedure reported previously (Aoyagi et al, 1983;Miyazaki et al, 2012). In brief, wild fruiting bodies of G. junonius were lyophilized, crunched and stored at -20 ºC.…”
Section: Isolation and Purification Of Gymnopilinsmentioning
confidence: 99%
“…We have recently reported that gymnopilins activate phospholipase C and increase intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in non-neuronal cells isolated from dorsal root ganglia of the rat (Miyazaki et al, 2012), and that gymnopilins act directly on vascular smooth muscles and activated the cAMP-dependent cascade to cause the vasodilation (Nishio et al, 2012). However, direct evidence that gymnopilins act on neurons is still lacking.…”
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.
“…We have recently reported that gymnopilins activate two intracellular signal cascades including the phospholipase C-dependent one (Miyazaki et al, 2012) and the cAMP-dependent one (Nishio et al, 2012). In addition, here we report that gymnopilins act on the nAChR.…”
Section: Junoniussupporting
confidence: 65%
“…Gymnopilins were purified from the wild fruiting body of G. junonius collected in Japan according to the procedure reported previously (Aoyagi et al, 1983;Miyazaki et al, 2012). In brief, wild fruiting bodies of G. junonius were lyophilized, crunched and stored at -20 ºC.…”
Section: Isolation and Purification Of Gymnopilinsmentioning
confidence: 99%
“…We have recently reported that gymnopilins activate phospholipase C and increase intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in non-neuronal cells isolated from dorsal root ganglia of the rat (Miyazaki et al, 2012), and that gymnopilins act directly on vascular smooth muscles and activated the cAMP-dependent cascade to cause the vasodilation (Nishio et al, 2012). However, direct evidence that gymnopilins act on neurons is still lacking.…”
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.
“…Recently, we reported that gymnopilins activated Gq-coupled GPCRs expressed in neurons and glial cells in dorsal root ganglia and cerebral cortex. 7) Gymnopilins may be distributed into the central nervous system crossing the blood brain barrier and may act directly on cells in the central nervous system to excite the vasomotor center. Underlying mechanisms including this possibility need to be examined in the future study.…”
Section: Fig 4 Effects Of Sq-22536 On the Vasodilating Effect Of Gymentioning
confidence: 99%
“…Recently, we reported that gymnopilins act on mammalian neurons and glial cells. 7) Gymnopilins are likely to bind to some G protein-coupled receptor and mobilize cytosolic Ca 2+ from the intracellular Ca 2+ store. When fruiting bodies of G. junonius are ingested, gymnopilins are absorbed in the gastrointestinal tract and carried into the blood.…”
Gymnopilin is one of the substances produced by the hallucinogenic mushroom, Gymnopilus junonius. In this study, we examined effects of gymnopilins purified from wild fruiting bodies of G. junonius on contractile activity of aorta preparations and blood pressure in rats. Gymnopilins at lower concentrations than 5 mg/mL did not evoke contraction of helical strips of the thoracic aorta. In contrast, gymnopilins (5 mg/ mL) applied to the aorta strips pre-contracted by norepinephrine (100 nM) caused relaxation. This relaxing action did not depend on the activity of the endothelium cells. The relaxing effect of 5-mg/mL gymnopilins was observed in aorta strips contracted by angiotensin II (10 nM) and the high K solution (60 mM). Moreover, the adenylyl cyclase inhibitor, SQ-22536, significantly inhibited the relaxing effect of gymnopilins at 1 mg/mL on the norepinephrine-contracted strips. These results suggested that gymnopilins acted directly on smooth muscle cells of the aorta and activated the cAMP-dependent cascade to cause the vasodilation. Paradoxically, gymnopilins injection into the jugular vein transiently increased blood pressure without affecting the heart rate. This result suggests that gymnopilins increase cardiac output and/or tension of the artery through the excitation of the vasomotor nerve that overcame the direct relaxing effect on the vascular smooth muscle.
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