Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Chen, Xuechai; Arshad, Abida; Qing, Hong; Wang, Rui; Lu, Jianqing; Deng, Yulin

doi:10.2478/s11756-011-0134-y

Cited by 20 publications

(13 citation statements)

References 17 publications

(15 reference statements)

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“…A further line of experimental evidence, though yet speculative, of the involvement of DA in the effects of ACD originates from the studies on the condensation product(s) of ACD which, in particular when condensates with DA, can either spontaneously and enzymatically (Chen et al, 2011) generate 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol) (Yamanaka et al, 1970; Jamal et al, 2003). Interestingly, since its discovery, this molecule has been related to ethanol (Davis and Walsh, 1970; Davis et al, 1970) and it was hypothesized that at least the DA-mediated effects of ethanol could be attributed to salsolinol (Davis and Walsh, 1970; Davis et al, 1970).…”

Section: Acetaldehyde Dopamine and Intracellular Signalingmentioning

confidence: 99%

Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Peana¹,

Acquas²

2013

Front. Behav. Neurosci.

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Since Chevens' report, in the early 50's that his patients under treatment with the aldehyde dehydrogenase inhibitor, antabuse, could experience beneficial effects when drinking small volumes of alcoholic beverages, the role of acetaldehyde (ACD) in the effects of ethanol has been thoroughly investigated on pre-clinical grounds. Thus, after more than 25 years of intense research, a large number of studies have been published on the motivational properties of ACD itself as well as on the role that ethanol-derived ACD plays in the effects of ethanol. Accordingly, in particular with respect to the motivational properties of ethanol, these studies were developed following two main strategies: on one hand, were aimed to challenge the suggestion that also ACD may exert motivational properties on its own, while, on the other, with the aid of enzymatic manipulations or ACD inactivation, were aimed to test the hypothesis that ethanol-derived ACD might have a role in ethanol motivational effects. Furthermore, recent evidence significantly contributed to highlight, as possible mechanisms of action of ACD, its ability to commit either dopaminergic and opioidergic transmission as well as to activate the Extracellular signal Regulated Kinase cascade transduction pathway in reward-related brain structures. In conclusion, and despite the observation that ACD seems also to have inherited the elusive nature of its parent compound, the behavioral and biochemical evidence reviewed points to ACD as a neuroactive molecule able, on its own and as ethanol metabolite, to exert motivational effects.

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Section: Acetaldehyde Dopamine and Intracellular Signalingmentioning

confidence: 99%

Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Peana¹,

Acquas²

2013

Front. Behav. Neurosci.

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“…), and is a highly reactive molecule, which may condensate, either spontaneously or enzymatically (Chen et al . ), with nucleophilic compounds, such as monoamines, to produce tetrahydroisoquinolines. When condensates with DA, acetaldehyde generates 1‐methyl‐6,7‐dihydroxy‐1,2,3,4‐tetrahydroisoquinoline (salsolinol) (Yamanaka, Walsh & Davis ; Jamal et al .…”

Section: Introductionmentioning

confidence: 99%

“…; Chen et al . ), we hypothesized that salsolinol might be involved in ethanol stimulatory action on pVTA DA cells. The present study was designed to challenge this hypothesis by recording pVTA DA cell firing in acute brain slices ex vivo in which somatodendritic DA release was reduced (Cheramy, Leviel & Glowinski ) by in vivo administration of α‐methyl‐p‐tyrosine (αMpT) or reserpine.…”

Section: Introductionmentioning

confidence: 99%

Key role of salsolinol in ethanol actions on dopamine neuronal activity of the posterior ventral tegmental area

et al. 2013

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Ethanol excites dopamine (DA) neurons in the posterior ventral tegmental area (pVTA). This effect is responsible for ethanol's motivational properties and may contribute to alcoholism. Evidence indicates that catalase-mediated conversion of ethanol into acetaldehyde in pVTA plays a critical role in this effect. Acetaldehyde, in the presence of DA, condensates with it to generate salsolinol. Salsolinol, when administered in pVTA, excites pVTA DA cells, elicits DA transmission in nucleus accumbens and sustains its self-administration in pVTA. Here we show, by using ex vivo electrophysiology, that ethanol and acetaldehyde, but not salsolinol, failed to stimulate pVTA DA cell activity in mice administered α-methyl-p-tyrosine, a DA biosynthesis inhibitor that reduces somatodendritic DA release. This effect was specific for ethanol and acetaldehyde since morphine, similarly to salsolinol, was able to excite pVTA DA cells in α-methyl-p-tyrosine-treated mice. However, when DA was bath applied in slices from α-methyl-p-tyrosine-treated mice, ethanol-induced excitation of pVTA DA neurons was restored. This effect requires ethanol oxidation into acetaldehyde given that, when H2 O2 -catalase system was impaired by either 3-amino-1,2,4-triazole or in vivo administration of α-lipoic acid, ethanol did not enhance DA cell activity. Finally, high performance liquid chromatography-tandem mass spectrometry analysis of bath medium detected salsolinol only after co-application of ethanol and DA in α-methyl-p-tyrosine-treated mice. These results demonstrate the relationship between ethanol and salsolinol effects on pVTA DA neurons, help to untangle the mechanism(s) of action of ethanol in this area and contribute to an exciting research avenue prosperous of theoretical and practical consequences.

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“…However, the exact pathogenesis mechanism of this vicious cycle in PD is still not clear. Recently, Deng's group confirmed the existence of Sal synthetase, that is a thermostable enzyme, and the higher enzymatic condensation reaction of DA and acetaldehyde was detected in the striatum and substantia nigra of rat brains [22,23]. Of CTIQs, Sal is a representative neurotoxin, which presents a high level in brains of PD patients and has been shown to increase ROS, inhibit mitochondrial function and cell injury [24][25][26].…”

Section: Endogenous Catechol Tetrahydroisoquinolinesmentioning

confidence: 99%

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

Chen¹,

Lu²,

Duan³

et al. 2017

J Alzheimers Dis Parkinsonism

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Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Cited by 20 publications

References 17 publications

Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Behavioral and biochemical evidence of the role of acetaldehyde in the motivational effects of ethanol

Key role of salsolinol in ethanol actions on dopamine neuronal activity of the posterior ventral tegmental area

Catechol Tetrahydroisoquinolines Enhance a-Synuclein Aggregation and Specify the Neurotoxicity to Dopaminergic Neurons

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