Valoti M, Benocci A, Marazova K, Mantovani P
Institute of Pharmacological Sciences, School of Pharmacy, University of Siena, Italy.
Pharmacol Res. 1996 Nov-Dec;34(5-6):219-24. doi: 10.1006/phrs.1996.0091.
Carnitine is a natural substance that acts as a carrier of fatty-acids across the inner mitochondrial membrane for subsequent beta-oxidation. Acetyl-L-carnitine is the acetyl derivative of L-carnitine that has been shown to possess a slight cholinomimetic activity. Its success in sports medicine is dependent on the fact that it is able to stimulate the central nervous system functions. This study aims to investigate the effects of L-carnitine (LC) and its derivatives-acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC)-on gastric acid secretion in rats. A concentration-dependent relationship with both ALC or PLC was observed in experiments in vitro using a rat isolated stomach. The addition of atropine to the perfusion bath only partially antagonized the effects of the two compounds. Stimulation of gastric acid secretion in a dose-dependent manner was also found when the tested compounds were administered i.v. to anaesthetized rats. To elucidate the mechanism of the gastric secretory response, assay for acetylcholine esterase activity using acetylthiocholine as substrate, was performed. It was found that ALC and PLC inhibited acetylcholine esterase, however, the IC50 for both compounds was about four times of magnitude greater than that of eserine. As the increase of the gastric acid secretion promoted by carnitines was blocked only partially by atropine both in vitro and in vivo, whilst it was completely abolished by experimental degeneration of the sympathetic neurons or by blockade of the postsynaptic sympathetic receptors, it is suggested that the effect of carnitines is determined by cholinergic and partly by adrenergic mechanisms.
肉碱是一种天然物质，作为脂肪酸穿过线粒体内膜的载体，随后进行β-氧化。乙酰-L-肉碱是L-肉碱的乙酰衍生物，已被证明具有轻微的拟胆碱活性。它在运动医学中的成功取决于它能够刺激中枢神经系统功能这一事实。本研究旨在探讨L-肉碱（LC）及其衍生物——乙酰-L-肉碱（ALC）和丙酰-L-肉碱（PLC）对大鼠胃酸分泌的影响。在使用大鼠离体胃的体外实验中，观察到ALC或PLC与胃酸分泌存在浓度依赖关系。向灌注浴中加入阿托品仅部分拮抗了这两种化合物的作用。当将受试化合物静脉注射给麻醉大鼠时，也发现它们以剂量依赖方式刺激胃酸分泌。为了阐明胃酸分泌反应的机制，使用乙酰硫代胆碱作为底物进行了乙酰胆碱酯酶活性测定。发现ALC和PLC抑制乙酰胆碱酯酶，然而，这两种化合物的半数抑制浓度（IC50）比毒扁豆碱约大四倍。由于在体外和体内，肉碱促进的胃酸分泌增加仅部分被阿托品阻断，而通过交感神经元的实验性变性或突触后交感受体的阻断可完全消除这种增加，因此表明肉碱的作用由胆碱能机制决定，部分由肾上腺素能机制决定。
