Cooper R A, de Freitas J C, Porreca F, Eisenhour C M, Lukas R, Huxtable R J
Department of Pharmacology, College of Medicine, University of Arizona, Tucson 85724, USA.
Toxicon. 1995 Aug;33(8):1025-31. doi: 10.1016/0041-0101(95)00047-p.
Caissarone, a sea anemone iminopurine, produced an increase in the twitch response of the electrically stimulated guinea-pig ileum-myenteric plexus. In the same assay, caissarone reduced the inhibitory response to the endogenous neuromodulator, adenosine, the A1 adenosine receptor agonist, R-phenylisopropyladenosine (R-PIA), and the A2 agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA) in a dose-dependent manner. Schild plot analysis of antagonism by caissarone yielded slopes of near unity, indicating that caissarone acts as a simple competitive antagonist at the adenosine receptor. The dissociation constants (KB) for caissarone ranged from 0.53 mM to 0.78 mM. In functional nicotinic receptor assays in two human cell lines, caissarone failed either to potentiate or to reduce carbamylcholine-mediated 86Rb+ efflux. Thus, the enhancing activity of caissarone on the gut could not be attributed to activity at the ganglionic nicotinic receptor. Based on structure and pharmacological activity, caissarone appears to be the first marine product described as an adenosine receptor antagonist.
海葵亚胺嘌呤卡西萨罗宁可使电刺激的豚鼠回肠 - 肌间神经丛的抽搐反应增强。在同一实验中，卡西萨罗宁能剂量依赖性地降低对内源性神经调节剂腺苷、A1 型腺苷受体激动剂 R - 苯异丙基腺苷（R - PIA）以及 A2 型激动剂 5'-（N - 环丙基）- 羧酰胺腺苷（CPCA）的抑制反应。对卡西萨罗宁拮抗作用的希尔德作图分析得出斜率接近 1，表明卡西萨罗宁在腺苷受体上作为一种简单的竞争性拮抗剂起作用。卡西萨罗宁的解离常数（KB）范围为 0.53 mM 至 0.78 mM。在两种人类细胞系的功能性烟碱样受体实验中，卡西萨罗宁既不能增强也不能降低氨甲酰胆碱介导的 86Rb + 外流。因此，卡西萨罗宁对肠道的增强活性不能归因于对神经节烟碱样受体的活性。基于结构和药理活性，卡西萨罗宁似乎是被描述为腺苷受体拮抗剂的首个海洋产物。
