Neumann Joachim, Dimov Kiril, Azatsian Karyna, Hofmann Britt, Gergs Ulrich
Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle D-06097, Germany.
Institute for Pharmacology and Toxicology, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle D-06097, Germany; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Gdansk, Poland.
Toxicol Lett. 2024 Jul;398:55-64. doi: 10.1016/j.toxlet.2024.06.006. Epub 2024 Jun 12.
Several fungi belonging to the genus Psilocybe, also called "magic mushrooms", contain the hallucinogenic drugs psilocybin and psilocin. They are chemically related to serotonin (5-HT). In addition to being abused as drugs, they are now also being discussed or used as a treatment option for depression. Here, we hypothesized that psilocybin and psilocin may act also on cardiac serotonin receptors and studied them in vitro in atrial preparations of our transgenic mouse model with cardiac myocytes-specific overexpression of the human 5-HT receptor (5-HT-TG) as well as in human atrial preparations. Both psilocybin and psilocin enhanced the force of contraction in isolated left atrial preparations from 5-HT-TG, increased the beating rate in isolated spontaneously beating right atrial preparations from 5-HT-TG and augmented the force of contraction in the human atrial preparations. The inotropic and chronotropic effects of psilocybin and psilocin at 10 µM were smaller than that of 1 µM 5-HT on the left and right atria from 5-HT-TG, respectively. Psilocybin and psilocin were inactive in WT. In the human atrial preparations, inhibition of the phosphodiesterase III by cilostamide was necessary to unmask the positive inotropic effects of psilocybin or psilocin. The effects of 10 µM psilocybin and psilocin were abrogated by 10 µM tropisetron or by 1 µM GR125487, a more selective 5-HT receptor antagonist. In summary, we demonstrated that psilocin and psilocybin act as agonists on cardiac 5-HT receptors.
几种属于裸盖菇属的真菌，也被称为“神奇蘑菇”，含有致幻药物裸盖菇素和脱磷酸裸盖菇素。它们在化学结构上与血清素（5-羟色胺）相关。除了作为毒品被滥用外，它们目前也被讨论或用作治疗抑郁症的一种选择。在此，我们推测裸盖菇素和脱磷酸裸盖菇素可能也作用于心脏血清素受体，并在我们构建的人类5-羟色胺受体（5-HT）在心肌细胞中特异性过表达的转基因小鼠模型的心房制剂以及人类心房制剂中进行了体外研究。裸盖菇素和脱磷酸裸盖菇素均增强了5-HT转基因小鼠离体左心房制剂的收缩力，提高了5-HT转基因小鼠离体自发搏动右心房制剂的搏动频率，并增强了人类心房制剂的收缩力。10µM的裸盖菇素和脱磷酸裸盖菇素对5-HT转基因小鼠左、右心房的变力性和变时性作用分别小于1µM 5-羟色胺的作用。裸盖菇素和脱磷酸裸盖菇素对野生型小鼠无活性。在人类心房制剂中，西洛酰胺抑制磷酸二酯酶III对于揭示裸盖菇素或脱磷酸裸盖菇素的正性变力作用是必要的。10µM的托烷司琼或1µM的GR125487（一种更具选择性的5-羟色胺受体拮抗剂）可消除10µM裸盖菇素和脱磷酸裸盖菇素的作用。总之，我们证明脱磷酸裸盖菇素和裸盖菇素可作为心脏5-羟色胺受体的激动剂。
