Multiple Effects of Gymnopilin on Circulatory System of the Rat

Abstract

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.

Gymnopilins, a product of a hallucinogenic mushroom, inhibit the nicotinic acetylcholine receptor

“…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.…”

“…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.…”

Mushroom Toxins: Chemistry and Toxicology

“…The multiple effects on the various tissues and cell types may relate to different gymnopilin molecules. 154 Recently, gymnopilins have been found to directly bind to and inhibit nicotinic types of acetylcholine (Ach) receptors, which may partially explain Gs. spectabilis poisoning.…”

“…Gymnopilins may be distributed into the central nervous system by crossing the blood–brain barrier and could act directly on cells in the central nervous system to excite the vasomotor center. The multiple effects on the various tissues and cell types may relate to different gymnopilin molecules . Recently, gymnopilins have been found to directly bind to and inhibit nicotinic types of acetylcholine (Ach) receptors, which may partially explain Gs.…”