Llansola M, Felipo V
Instituto de Investigaciones Citológicas de la Fundación Valenciana de Investigaciones Biomédicas, Valencia, Spain.
Neurochem Res. 1998 Dec;23(12):1533-7. doi: 10.1023/a:1020928020469.
We previously found that carnitine prevents glutamate neurotoxicity and that this effect is mediated by activation of metabotropic glutamate receptors. We show now that carnitine inhibits the hydrolysis of inositol phospholipids induced by different agonists of metabotropic glutamate receptors (tACPD; (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid; DHPG, (R,S)-3,5-dyhydroxyphenylglycine or S4C3HPG, (S)-4-carboxy-3-hydroxyphenylglycine). The EC50 was ca. 170 microM and the inhibition was complete at 1 mM carnitine. Carnitine also inhibits completely hydrolysis of inositol phospholipids induced by arterenol (agonist of adrenoceptors) and only partially (ca. 50%) that induced by carbachol (agonist of muscarinic receptors). Carnitine did not inhibit phospholipase C activity but inhibits partially (43%) the hydrolysis of inositol phospholipids induced by direct activation of G proteins with AIF4-. The results reported indicate that carnitine inhibits the hydrolysis of inositol phospholipids induced by activation of metabotropic receptors likely by interfering the function of some types of G proteins.
我们之前发现肉碱可预防谷氨酸神经毒性，且该作用是由代谢型谷氨酸受体的激活介导的。我们现在表明，肉碱可抑制由代谢型谷氨酸受体的不同激动剂（反式-ACPD；（±）-1-氨基环戊烷-反式-1,3-二羧酸；DHPG，（R,S）-3,5-二羟基苯甘氨酸或S4C3HPG，（S）-4-羧基-3-羟基苯甘氨酸）诱导的肌醇磷脂水解。半数有效浓度约为170微摩尔，在1毫摩尔肉碱时抑制作用完全。肉碱还可完全抑制去甲肾上腺素（肾上腺素能受体激动剂）诱导的肌醇磷脂水解，而对卡巴胆碱（毒蕈碱受体激动剂）诱导的水解仅部分抑制（约50%）。肉碱不抑制磷脂酶C活性，但部分抑制（43%）由AIF4-直接激活G蛋白诱导的肌醇磷脂水解。报道的结果表明，肉碱可能通过干扰某些类型G蛋白的功能来抑制由代谢型受体激活诱导的肌醇磷脂水解。
