Conversion of 3,4‐Dihydroxyphenylalanine and Deuterated 3,4‐Dihydroxyphenylalanine to Alcoholic Metabolites of Catecholamines in Rat Brain

Abstract

We have investigated the effects of 3, 4-dihydroxyphenylalanine (L-DOPA) and its deuterated analogue on the concentrations of alcoholic metabolites of catecholamines in rat brain by means of gas chromatography/mass spectrometry with selected-ion monitoring. Whole brain concentrations of the two neutral norepinephrine metabolites, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3, 4-dihydroxyphenylethyleneglycol (DHPG), were significantly increased in a dose-dependent manner by a single intraperitoneal injection of L-DOPA. Both MHPG and DHPG, as well as the corresponding dopamine metabolites, reached a maximum 1 h after injection. Brain MHPG and DHPG concentrations were elevated by 78 and 134%, respectively, 1 h after injection of 150 mg/kg L-DOPA. Analyses of discrete brain regions revealed that concentrations of the norepinephrine metabolites were elevated uniformly in all regions, except that MHPG showed a greater increase in the cerebellum than in other regions. The latter result appeared to be explained by the finding that 52% of the total MHPG in the cerebellum was unconjugated (compared to 15% in the whole brain). L-DOPA caused a proportionately greater increase in free MHPG than in total MHPG in the cerebellum and brain stem. By using deuterated L-DOPA in place of L-DOPA and measuring both the deuterated and nondeuterated norepinephrine metabolites, we demonstrated that virtually all of the increases in MHPG and DHPG were due to the conversion of the exogenous L-DOPA to norepinephrine. Thus, the effects of norepinephrine metabolism need to be considered in attempts to understand clinical and behavioral effects of L-DOPA.

Modification of dopamine and norepinephrine metabolism in the rat brain by monoamine oxidase inhibitors

“…As reported earlier L-dopa treatment alone considerably raised DA levels in the hypothalamus and brain stem but did not change NE concentrations. This finding differs from that of Chalmers et al (1971), who used a fluorometric method to determine NE, but agree with most recent reports (Freed and Murphy, 1978;Edwards and Rizk, 1981;Commissiong, 1984), which used the highly specific GC-MS method to measure NE. NE failed to increase even when DA was injected intraventricularly to give concentrations …”

“…On the other hand, as Table 1 indicates, L-dopa treatment led to a moderate increase in MHPG, and this increase was dose-dependent. Edwards and Rizk (1981) reported a similar dose-dependent response of whole brain MHPG to L-dopa administration. Our MHPG values in the hypothalamus and brain stem measured by the present HPLC method are similar to the values obtained by these authors, by GC-MS, which suggests that the HPLC method (Westerink, 1984) is specific.…”

Metabolism of Catecholamines in the Developing Spinal Cord of the Rat

“…The earliest time studied was 1 h, so it is possible, but unlikely, that a transient increase in NE did occur before 1 h. However, there is an increase in NE synthesis, which is reflected in a sharp increase in MHPG at 1 h in all regions (Fig. 3) (see also Edwards et al, 1981;Edwards and Rizk, 1981).…”

Hydroxytyrosol: from laboratory investigations to future clinical trials

“…It has been shown that HT can cross the blood‐brain barrier to appear in the brain, although it must be taken into account that HT may be generated endogenously from dihydroxyphenylacetic acid through dihydroxyphenylacetic reductase of the brain 39 . It can also be generated from dopamine 40 . De la Torre 29 has suggested that our understanding of the function of HT is hampered by the fact that HT is a metabolite of dopamine and that the HT concentration in body fluids is a combination of the exogenous and endogenous sources.…”

“…39 It can also be generated from dopamine. 40 De la Torre 29 has suggested that our understanding of the function of HT is hampered by the fact that HT is a metabolite of dopamine and that the HT concentration in body fluids is a combination of the exogenous and endogenous sources. This is the main reason it is not possible to mini-mize its concentration in biological fluids, hindering the evaluation of its availability in the organism, whether after a period without food intake or after strict dietary control.…”