Role of acetaldehyde in tobacco smoke addiction.

This review evaluates the presumed contribution of acetaldehyde to tobacco smoke addiction. In rodents, acetaldehyde induces reinforcing effects, and acts in concert with nicotine. Harman and salsolinol, condensation products of acetaldehyde and biogenic amines, may be responsible for the observed reinforcing effect of acetaldehyde. Harman and salsolinol inhibit monoamine oxidase (MAO), and some MAO-inhibitors are known to increase nicotine self-administration and maintain behavioural sensitization to nicotine. Harman is formed in cigarette smoke, and blood harman levels appear to be 2-10 times higher compared to non-smokers. Since harman readily passes the blood-brain barrier and has sufficient MAO-inhibiting potency, it may contribute to the lower MAO-activity observed in the brain of smokers. In contrast, the minor amounts of salsolinol that can be formed in vivo most likely do not contribute to tobacco addiction. Thus, acetaldehyde may increase the addictive potential of tobacco products via the formation of acetaldehyde-biogenic amine adducts in cigarette smoke and/or in vivo, but further research is necessary to substantiate this hypothesis.

Fluorometric determination of 1,2,3,4-tetrahydro-6,7-dihydroxyisoquinoline in biological materials by HPLC.

In the belief that endogenous 1,2,3,4-tetrahydro-6,7-dihydroxyisoquinoline (DA-Fp) could be a potential marker involved in the etiology of various diseases such as Parkinsonism, we attempted to develop a fluorescence method for DA-Fp. It was synthesized by condensation of dopamine with formaldehyde according to an established method. Periodate was identified by screening from various oxidation reagents as a fluorescence reagent to DA-Fp. Optimal reaction conditions were obtained with 0.25 mM NaIO4 in 0.1 M phosphate buffer (pH 8.0) at 37 degrees C for 15 min. The fluorescence spectrum of the derivative showed that we had found a new reaction specific for DA-Fp. This reaction was coupled on-line to high performance liquid chromatography (HPLC), which enabled us to achieve a highly sensitive method for determining DA-Fp. A working curve was linear from 2 to 800 pmol of DA-Fp per injection. To determine DA-Fp in biological materials, the pretreatment before HPLC was optimized by hydrolysis of its conjugate and suppression of the artifact with l-phenylephrine. Urinary excretion of DA-Fp in men was measured by this new present method. The urinary excretion of endogenous DA-Fp increased in a rabbit given L-DOPA. The DA-Fp concentration was determined in rat brain. The significance of DA-Fp in these biological materials is discussed and evaluated. We conclude that the present method will be useful for studying tetrahydroisoquinolines involved in many diseases.

Detection of endogenous salsolinol in neonatal rat tissue by a radioenzymatic--thin-layer chromatographic assay.

A sensitive radioenzymaticc--thin-layer chromatographic assay for the quantitative analysis of the tetrahydroisoquinoline alkaloid, salsolinol, in plasma and neonatal rat tissue is described. The assay involves the enzymatic O-methylation of salsolinol by catechol-O-methyltransferase in presence of [3H]S-adenosylmethionine, and subsequent separation by thin-layer chromatography of the resultant [3H]O-methyl-salsolinol from the O-methylated derivatives of dopamine, epinephrine and norepinephrine. The method allows the detection of as little as 100 pg salsolinol per g tissue, and the accurate quantitation of as little as 100 pg/ml plasma and 500 pg/g tissue. This assay permitted the detection of trace amounts of endogenous salsolinol in neonatal rat tissue (less than 500 pg/g tissue).