β-N-草酰-α,β-二氨基丙酸（β-ODAP）三种结构类似物的神经毒性潜力。
Neurotoxic potential of three structural analogs of beta-N-oxalyl-alpha,beta-diaminopropanoic acid (beta-ODAP).
作者信息
Omelchenko I A, Jain R K, Junaid M A, Rao S L, Allen C N
机构信息
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201-3098, USA.
出版信息
Neurochem Res. 1999 Jun;24(6):791-7. doi: 10.1023/a:1020791815848.
Lathyrism is a non-progressive motor neuron disease produced by consumption of the excitatory amino acid, 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP). To learn more about the mechanisms underlying Lathyrism three structural analogs of beta-ODAP were synthesized. Carboxymethyl-alpha,beta-diaminopropanoic acid (CMDAP) evoked inward currents which were antagonized by APV (30 microM), but not by CNQX (10 microM). N-acetyl-alpha,beta-diaminopropanoic acid (ADAP) evoked no detectable ionic currents but potentiated N-methyl-D-aspartate (NMDA)-activated currents. The potentiation of NMDA currents by ADAP was blocked by 7-chlorokynurenic acid. Carboxymethylcysteine (CMC) did not activate any detectable ionic currents. None of the three beta-ODAP analogs produced visible symptoms of toxicity in day old chicks when administered for 2-3 consecutive days. Ligand binding studies demonstrated that all the three compounds were effective to in displacing [3H]glutamate. The maximum inhibition was 92% for CMDAP, 61% for ADAP, 65% for CMC and 99% for beta-ODAP. These data indicate that analogs of beta-ODAP may interact with glutamate receptors without producing neurotoxicity.
山黧豆中毒是一种由食用兴奋性氨基酸3 - N -草酰基-L - 2,3 -二氨基丙酸（β-ODAP）引起的非进行性运动神经元疾病。为了更多地了解山黧豆中毒的潜在机制，合成了β-ODAP的三种结构类似物。羧甲基-α,β-二氨基丙酸（CMDAP）诱发内向电流，该电流可被APV（30 microM）拮抗，但不被CNQX（10 microM）拮抗。N - 乙酰-α,β-二氨基丙酸（ADAP）未诱发可检测到的离子电流，但增强了N -甲基-D -天冬氨酸（NMDA）激活的电流。ADAP对NMDA电流的增强作用被7 -氯犬尿氨酸阻断。羧甲基半胱氨酸（CMC）未激活任何可检测到的离子电流。连续2 - 3天给一日龄雏鸡施用这三种β-ODAP类似物，均未产生明显的毒性症状。配体结合研究表明，这三种化合物都能有效地置换[3H]谷氨酸。CMDAP的最大抑制率为92%，ADAP为61%，CMC为65%，β-ODAP为99%。这些数据表明，β-ODAP类似物可能与谷氨酸受体相互作用而不产生神经毒性。
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