On the recovery of [3H]noradrenaline from different metabolic compartments of rat brain with respect to the role of catechol-O-methyltransferase

Abstract

Rats were treated with reserpine, desmethyl-imipramine, or carrier, either alone or in combination with tropolone. Either 10 min (t1) or 1 h (t2) after intraventricular injection of [3H]noradrenaline, they were decapitated. The total 3H activity and the recovery of [3H]noradrenaline were determined in tissue extracts from various brain regions. Maximum total 3H activity was measured at t1 in all tropolone-treated rats; the mean sum of these results served as an estimate of the initial tissue concentration of [3H]noradrenaline. At t1, 40-50% of the sum of [3H]noradrenaline and its metabolites was recovered unchanged in normal rats; reserpine and DMI reduced the recovery to 18-27%. In all groups, the decline of [3H]noradrenaline was retarded after t1. Inhibition of catechol-O-methyltransferase by tropolone caused consistently elevated [3H]noradrenaline levels, but did not affect the metabolic rate after t1 when compared with similarly pretreated, but tropolone-free rats. Thus, if catechol-O-methyltransferase was inhibited during the injection of [3H]noradrenaline, a higher percentage of the amine had been taken up into spaces with a slow noradrenaline turnover. The maximum increase was seen when the neuronal uptake1 was inhibited by desmethylimipramine. This supported the hypothesis that an additional extraneuronal space exists, in addition to the known intraneuronal and extraneuronal compartments, which has a slow noradrenaline turnover. The tropolone effect on the noradrenaline recovery possibly shows that there might be a saturable "methylating system," similar to that described for the periphery, in which catechol-O-methyltransferase is linked to the extraneuronal uptake2.(ABSTRACT TRUNCATED AT 250 WORDS)