Metabolism Of Norepinephrine In Rat Brain Research Articles

Is 3,4-dihydroxyphenylglycol the major route of central norepinephrine metabolism in rat brain?

Central norepinephrine (NE) metabolism was assessed by measuring 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and 3,4-dihydroxyphenylethyleneglycol (DHPG) in different rat brain areas after saline or probenecid (300 mg/kg) administration. Under probenecid, results showed an increased accumulation of total MHPG and DHPG, and a clear preponderance of DHPG levels over MHPG in almost all the brain areas examined. Estimation of their formation rates confirmed that in basal conditions DHPG is formed more rapidly. This study supports the notion that, without ruling out the importance of MHPG, brain DHPG may be a useful index of central NE activity.

The effects of L-threo-dihydroxyphenylserine on norepinephrine metabolism in rat brain

The effects of L- threo-3,4-dihydroxyphenylserine (DOPS), an artificial precursor of norepinephrine (NE), on NE metabolism in rat brain were investigated. DOPS administration resulted in a significant elevation in cerebral NE and 3-methoxy-4-hydroxyphenylglycol contents, while carbidopa pretreatment completely blocked these increases. After brain NE was depleted by either α-methyl- p-tyrosine (AMPT), fusaric acid, FLA-63, or reserpine, NE restoration by DOPS was observed in rats treated with either fusaric acid or chronic reserpine. No NE restoration was observed after pretreatment with AMPT, FLA-63, or acute reserpine. The results suggest that NE formed after DOPS administration is mainly localized in the brain capillaries. In some NE-depleting conditions, however, DOPS can penetrate the brain parenchyma.

Clonidine prevents methylxanthine stimulation of norepinephrine metabolism in rat brain.

Methylxanthines can produce behavior resembling opiate withdrawal in rats. Since previous studies have demonstrated the involvement of central noradrenergic systems during naloxone-precipitated withdrawal, the effects of 3-isobutyl-1-methylxanthine (IBMX) on norepinephrine metabolism in rat brain were studied. It was found that administration of IBMX elevated levels of the major norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in areas innervated by the locus coeruleus. The increases in MHPG was noted 1 h after administration and was maximal (270% of control) after 3 h. Levels of another norepinephrine metabolite, 3,4-dihydroxyphenylglycol, followed a similar pattern and time course. Coadministration of naloxone with IBMX did not affect the IBMX-induced elevation in MHPG. Administration of the alpha-agonist clonidine, however, antagonized the effects of IBMX on MHPG levels. The effects of IBMX and clonidine were dose dependent; the lowest dose of IBMX needed to elevate MHPG was 30 mumol/kg (i.p.), and clonidine (180 nmol/kg) reduced the effect of IBMX (100 mumol/kg) by 50%. The data, discussed in terms of a methylxanthine-noradrenergic interaction, suggest that withdrawal behaviors in general may be subserved by hyperactive noradrenergic neurons.

A study of norepinephrine metabolism in rat brain using a double label technique

Using a double-label procedure, the incorporation of endogenously-derived 35SO 4 into phenylethylene glycol sulfates (PGS) was estimated. When [ 3H]norepinephrine and [ 35S]cysteine were injected concomitantly into the brain, about 30–80 percent of the tritium and about 4 percent of the 35S retained in the brain 1 hr later were in PGS. In B 6-deficient rats, the proportion of 35S was increased as was the 35 S 3 H ratio. Probenecid caused a significant increase in the amount of PGS found in the brain, but a minimal enrichment of 35S was observed, suggesting that there was little or no effect on sulfotransferases. Cysteine in high concentrations inhibits the incorporation of tritium into PGS.