Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA.
Alcohol Clin Exp Res. 2010 Feb;34(2):242-50. doi: 10.1111/j.1530-0277.2009.01087.x. Epub 2009 Nov 24.
(R/S)-Salsolinol (SAL), a condensation product of dopamine (DA) with acetaldehyde, has been speculated to have a role in the etiology of alcoholism. Earlier studies have shown the presence of SAL in biological fluids and postmortem brains from both alcoholics and nonalcoholics. However, the involvement of SAL in alcoholism has been controversial over several decades, since the reported SAL levels and their changes after ethanol exposure were not consistent, possibly due to inadequate analytical procedures and confounding factors such as diet and genetic predisposition. Using a newly developed mass spectrometric method to analyze SAL stereoisomers, we evaluated the contribution of ethanol, diet, and genetic background to SAL levels as well as its enantiomeric distribution.
Simultaneous measurement of SAL enantiomers and DA were achieved by high performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS). Plasma samples were collected from human subjects before and after banana (a food rich in SAL) intake, and during ethanol infusion. Rat plasma and brain samples were collected at various time points after the administration of SAL or banana by gavage. The brain parts including nucleus accumbens (NAC) and striatum (STR) were obtained from alcohol-non-preferring (NP) or alcohol-preferring (P) rats as well as P-rats which had a free access to ethanol (P-EtOH).
Plasma SAL levels were increased significantly after banana intake in humans. Consistently, administration of banana to rats also resulted in a drastic increase of plasma SAL levels, whereas brain SAL levels remained unaltered. Acute ethanol infusion did not change SAL levels or R/S ratio in plasma from healthy humans. The levels of both SAL isomers and DA were significantly lower in the NAC of P rats in comparison to NP rats. The SAL levels in NAC of P rats remained unchanged after chronic free-choice ethanol drinking. There were decreasing trends of SAL in STR and DA in both brain regions. No changes in enantiomeric ratio were observed after acute or chronic ethanol exposure.
SAL from dietary sources is the major contributor to plasma SAL levels. No significant changes of SAL plasma levels or enantiomeric distribution after acute or chronic ethanol exposure suggest that SAL may not be a biomarker for ethanol drinking. Significantly lower SAL and DA levels observed in NAC of P rats may be associated with innate alcohol preference.
（R/S）-Salsolinol（SAL）是多巴胺（DA）与乙醛缩合的产物，据推测它在酒精中毒的病因学中起作用。早期的研究表明，SAL 存在于生物体液和酒精中毒者和非酒精中毒者的死后大脑中。然而，几十年来，SAL 对酒精中毒的影响一直存在争议，因为报告的 SAL 水平及其在乙醇暴露后的变化不一致，这可能是由于分析程序不充分以及饮食和遗传易感性等混杂因素造成的。我们使用新开发的质谱分析方法来分析 SAL 对映异构体，评估了乙醇、饮食和遗传背景对 SAL 水平及其对映体分布的贡献。
采用高效液相色谱-串联质谱法（HPLC/MS/MS）同时测定 SAL 对映异构体和 DA。从人类受试者摄入香蕉（富含 SAL 的食物）前后和输注乙醇期间采集血浆样本。给 SAL 或香蕉灌胃后，在不同时间点采集大鼠血浆和脑样本。从酒精不偏爱（NP）或酒精偏爱（P）大鼠以及有自由接触乙醇的 P 大鼠（P-EtOH）中获得包括伏隔核（NAC）和纹状体（STR）在内的脑区。
人类摄入香蕉后，血浆 SAL 水平显著升高。同样，给大鼠灌胃香蕉也导致血浆 SAL 水平急剧升高，而脑 SAL 水平保持不变。急性乙醇输注未改变健康人血浆中的 SAL 水平或 R/S 比值。与 NP 大鼠相比，P 大鼠 NAC 中的两种 SAL 异构体和 DA 水平均明显降低。慢性自由选择乙醇饮用后，P 大鼠 NAC 中的 SAL 水平保持不变。两个脑区的 SAL 和 DA 水平均呈下降趋势。急性或慢性乙醇暴露后，对映体比值无变化。
膳食来源的 SAL 是血浆 SAL 水平的主要贡献者。急性或慢性乙醇暴露后 SAL 血浆水平或对映体分布无明显变化表明，SAL 可能不是乙醇饮酒的生物标志物。P 大鼠 NAC 中 SAL 和 DA 水平明显降低可能与先天的酒精偏好有关。
