ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM

各种类型的受体和各种毒素用于调节离子 通道和产生第二信使，包括循环 核苷酸、二酰基甘油酯、花生四烯酸和磷脂酸。 易位后的钙、钠、钾和镁离子 通过离子通道或通过转运蛋白可以引起 释放过程，收缩蛋白，腺苷酸和鸟苷酸 环化酶、磷酸二酯酶、蛋白激酶、磷脂酶、ATP酶 和其他酶。 发生调节性相互作用或“串扰” 在第二信使系统和离子转运之间 系统. Maitotoxin是一种海洋聚醚， 在各种细胞中分解，显然是通过激活一种 膜钙通道 蝎毒激活的钙通道 似乎与任何已知的钙通道都不相同， 所谓钙释放激活钙（CRAC）通道，尽管 两个通道都被某些咪唑阻断（SKF 96365， 咪康唑、克霉唑）。 洛哌丁胺是一种 maitotoxin引起的通道阻滞剂，但会引起明显的 增强通过CRAC通道的流入， 受体介导的或毒胡萝卜素引起的IP 3-敏感性的耗竭 细胞内钙池存在于各种细胞类型中。 的 洛哌丁胺作用独特，高度依赖于结构， 容易被咪唑逆转。 甲基异恶唑类似物Epiboxidine 在神经节和中枢神经系统中， 神经元烟碱受体，是一种有效的兴奋剂， 与epibatidine相比毒性。 螺吡咯烷和 拟扑热息痛是一类新的非竞争性阻滞剂 尼古丁通道的 最有效的中心作用部位 据发现，假定的抗成瘾剂伊波替尼是非竞争性的 阻断神经节烟碱受体通道。 伊博阿是 高效对抗由中枢神经系统激活引发的镇痛 神经元烟碱受体 所有人的亲和力的轮廓 在不同的多巴胺和 测定去甲肾上腺素能受体。 其他研究涉及 生物胺包括儿茶酚-0- 人乳腺癌、仓鼠肾和大鼠甲基转移酶 牙髓

Receptors of various types and various toxins serve to modulate ion channels and generation of second messengers, including cyclic nucleotides, diacylglycerides, arachidonic acid and phosphatidic acid. Calcium, sodium, potassium, and magnesium ions after translocation through ion channels or by transport proteins can cause activation of release processes, contractile proteins, adenylate and guanylate cyclase, phosphodiesterases, protein kinases, phospholipases, ATPases and other enzymes. Modulatory interactions or "cross-talk" occurs both between the second messenger systems and the ion transport systems. Maitotoxin, a marine polyether, increases phosphoinositide breakdown in a variety of cells, apparently through activation of a membrane calcium channel. The maitotoxin-activated calcium channel does not appear identical to any know calcium-channel, including the so-called calcium release-activated calcium (CRAC) channel although both channels are blocked by certain imidazoles (SKF 96365, miconazole, clotrimazole). Loperamide is one of the most potent blockers of maitotoxin-elicited channels, but causes an apparent enhancement of influx through the CRAC-channels that open after receptor-mediated or thapsigargin-elicited depletion of IP3-sensitive intracellular pools of calcium in that a variety of cell types. The effect of loperamide is unique, high dependent on structure, and not readily reversed by imidazoles. Epiboxidine, a methylisoxazole analog of epibatidine, retains high activity at ganglionic and central neuronal nicotinic receptors and is a potent analgetic with reduced toxicity compared to epibatidine. Spiropyrrolizidines and pseudophrynaminol represent a new classes of noncompetitive blockers of nicotinic channels. The most potent central site of action of the putative antiaddictive agent ibogaine was found to be noncompetitive blockade of ganglionic nicotinic-receptor channels. Ibogaine was highly effective against analgesia triggered by activation of central neuronal nicotinic receptors. The profile of affinities of all possible ring-fluorinated dopamines at different dopamine and noradrenergic receptors was determined. Other studies involving biogenic amines include the localization and role of catechol-0- methyltransferase in human mammary carcinoma, hamster kidney and rat dental pulp.