ION CHANNELS, RECEPTORS AND SECOND MESSENGERS IN THE NERVOUS SYSTEM

各种类型的受体和各种毒素起着调节离子的作用 通道和第二信使的生成，包括循环 核苷酸、二酰甘油酯、花生四烯酸和磷脂酸。 易位后的钙、钠、钾和镁离子 通过离子通道或由运输蛋白引起的激活 释放过程、收缩蛋白、腺苷和鸟苷 环化酶、磷酸二酯酶、蛋白激酶、磷脂酶、三磷酸腺苷酶 和其他酶。调节性相互作用或“串扰”发生 在第二信使系统和离子传输之间 系统。毛霉毒素，一种海洋聚醚，增加磷脂酰肌醇 在各种细胞中分解，显然是通过激活一个 膜钙通道。毛霉毒素激活的钙通道 似乎与任何已知的钙通道不同，包括 所谓的钙释放激活钙(CRAC)通道 两个通道都被某些咪唑类化合物阻断(SKF 96365， 咪康唑、克霉唑)。洛哌丁胺是最有效的药物之一 毛霉毒素诱导的通道的阻断剂，但导致明显的 加强通过CRAC的流入--之后开放的渠道 受体介导或thapsigargin诱导的IP3敏感性耗竭 细胞内的钙池存在于各种细胞类型中。这个 洛哌丁胺的作用是独特的，高度依赖于结构，而不是 很容易被咪唑逆转。甲基异恶唑类似物--表巴西定 依巴替丁，在神经节细胞和中枢保持高活性 神经元尼古丁受体，是一种有效的止痛剂， 毒性与依巴替丁相比。螺吡咯里西定和 伪菲尼醇代表了一类新的非竞争性阻滞剂 尼古丁通道。世界上最强大的中心行动地点 推定的抗成瘾药伊博甘被发现是非竞争性的 阻断神经节细胞烟碱受体通道。伊博加因是 高效对抗中枢神经系统激活引起的镇痛 神经性烟碱受体。所有人的亲和力的轮廓 不同的多巴胺和可能的环氟多巴胺 测定去甲肾上腺素能受体。其他研究涉及 生物胺包括儿茶酚的定位和作用。 甲基转移酶在人乳腺癌、地鼠肾和大鼠肾脏中的表达 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.