NEW MOLLUSK-SPECIFIC ALPHA-CONOTOXINS BLOCK APLYSIA NEURONAL ACETYLCHOLINE-RECEPTORS
NEW MOLLUSK-SPECIFIC ALPHA-CONOTOXINS BLOCK APLYSIA NEURONAL ACETYLCHOLINE-RECEPTORS
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DOI：
10.1021/bi00198a018
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发表时间：
1994-08-16
期刊：
影响因子：
2.9
通讯作者：
ZLOTKIN, E
中科院分区：
文献类型：
--
作者：
FAINZILBER, M;HASSON, A;ZLOTKIN, E
描述了来自软体动物蜗牛 Conus pennaceus 毒液的两种软体动物特异性神经毒性肽。这些新毒素会阻断培养的海兔神经元的乙酰胆碱受体（AChR）。 0.5-1 μM 毒素的浴应用会诱导 5-10 mV 膜去极化，在毒素存在的情况下，膜去极化会在 1-3 分钟内恢复到对照水平。该反应可被 1 mM 六甲铵阻断。伴随着短暂的去极化，毒素阻断了大约 90% 的由短暂离子电渗应用乙酰胆碱引起的去极化反应。毒素（α PnIA、GCCSLPPCAANNPDYC-NH2；α PnIB、GCCSLPP-CALSNPDYC-NH2）的药理学和氨基酸序列使其归类为新型 α-芋螺毒素。这些序列与先前描述的α-芋螺毒素的序列在许多特征上有所不同，其中最引人注目的是C端环中存在单个带负电荷的残基。该环含有食鱼毒液α-芋螺毒素中带正电荷的残基。与其他对脊椎动物骨骼肌烟碱 ACh 受体具有选择性的 α-芋螺毒素相比，这些芋螺毒素可阻断软体动物中的神经元 ACh 受体。因此，它们是可用于定义 ACh 受体亚型的新探针，并且它们应该是研究 ACh 受体结构功能关系的有用工具。
Two mollusc-specific neurotoxic peptides from the venom of the molluscivorous snail Conus pennaceus are described. These new toxins block acetylcholine receptors (AChR) of cultured Aplysia neurons. Bath application of 0.5-1 mu M toxin induces 5-10-mV membrane depolarization, which recovers to the control level within 1-3 min in the presence of the toxin. This response is blocked by 1 mM hexamethonium. Concomitantly with the transient depolarization, the toxins block approximately 90% of the depolarizing responses evoked by brief iontophoretic application of acetylcholine. The pharmacology and amino acid sequences of the toxins (alpha PnIA, GCCSLPPCAANNPDYC-NH2; alpha PnIB, GCCSLPP-CALSNPDYC-NH2) enable their classification as novel alpha-conotoxins. The sequences differ from those of previously described alpha-conotoxins in a number of features, the most striking of which is the presence of a single negatively charged residue in the C-terminal loop. This loop contains a positively charged residue in piscivorous venom alpha-conotoxins. In contrast to other alpha-conotoxins, which are selective for vertebrate skeletal muscle nicotinic ACh receptors, these Conus pennaceus toxins block neuronal ACh receptors in molluscs. As such they are new probes which can be used to define subtypes of ACh receptors, and they should be useful tools in the study of structure-function relationships in ACh receptors.