Wehner J M, Marley R J
Exp Neurol. 1986 Nov;94(2):280-91. doi: 10.1016/0014-4886(86)90102-0.
delta-Aminolevulinic acid, an intermediate in heme formation, is elevated in certain human disorders including acute intermittent porphyria, tyrosinemia, and lead poisoning. It has been implicated in the central nervous system manifestations of these disorders via interactions with the GABAergic system. This potential interaction was examined by testing whether or not delta-aminolevulinic acid could alter the latency to seizure in mice. Seizures were induced in a variety of inbred strains of mice including C57BL, C3H, DBA mice and in a heterogeneous stock of mice. Flurothyl and 3-mercaptopropionic acid were used to induce seizures in the presence and absence of delta-aminolevulinic acid administered either i.p. (0.5 and 1.5 mmol/kg), or i.c.v. (4.5 and 450 nmol). delta-Aminolevulinic acid increased the latency to myoclonic and clonic seizures induced by flurothyl when administered i.p.; i.c.v. injections also delayed clonic seizures induced by flurothyl, and increased the latency to tonic seizures induced by 3-mercaptopropionic acid. The degree to which delta-aminolevulinic acid altered seizure latency in all tests was dependent on strain of mouse tested. These data support the conclusion that delta-aminolevulinic acid can act as an anticonvulsant agent, and mimic the effects of GABA. Moreover, there is genetic variation in the sensitivity of the various strains of mice to delta-aminolevulinic acid.
δ-氨基乙酰丙酸是血红素形成过程中的一种中间体，在某些人类疾病中会升高，包括急性间歇性卟啉病、酪氨酸血症和铅中毒。它通过与γ-氨基丁酸能系统相互作用，与这些疾病的中枢神经系统表现有关。通过测试δ-氨基乙酰丙酸是否能改变小鼠癫痫发作的潜伏期来研究这种潜在的相互作用。在多种近交系小鼠中诱导癫痫发作，包括C57BL、C3H、DBA小鼠以及一组杂种小鼠。在腹腔注射（0.5和1.5 mmol/kg）或脑室内注射（4.5和450 nmol）δ-氨基乙酰丙酸存在和不存在的情况下，使用氟烷和3-巯基丙酸诱导癫痫发作。腹腔注射δ-氨基乙酰丙酸可延长氟烷诱导的肌阵挛性和阵挛性癫痫发作的潜伏期；脑室内注射也可延迟氟烷诱导的阵挛性癫痫发作，并延长3-巯基丙酸诱导的强直性癫痫发作的潜伏期。在所有测试中，δ-氨基乙酰丙酸改变癫痫发作潜伏期的程度取决于所测试小鼠的品系。这些数据支持以下结论：δ-氨基乙酰丙酸可作为一种抗惊厥剂，并模拟γ-氨基丁酸的作用。此外，不同品系小鼠对δ-氨基乙酰丙酸的敏感性存在遗传差异。
