Metabolism of [3H]-noradrenaline in human dental pulp in vitro

Slices of pulp from human maxillary and mandibular molar and promolar teeth were incubated with [3H]-noradrenaline (0.2 mumol/l) for 30 min after which the [3H]-noradrenaline and [3H]-metabolites in the tissue and medium were assayed by column chromatography. The deaminated metabolites 3,4-dihydroxy phenyl glycol (DOPEG) and 3,4-dihydroxy mandelic acid (DOMA) constituted 81% of the metabolites formed. Cocaine, an inhibitor of uptake1, decreased the formation of DOPEG and DOMA as well as the accumulation of [3H]-noradrenaline. In contrast to findings in rabbit pulp, when the disposition of exogenous noradrenaline in human pulp was examined by monoamine fluorescence histochemistry there was no evidence of extraneuronal accumulation of noradrenaline by connective tissue cells. In further experiments, pulp that had been incubated in [3H]-noradrenaline (0.6 mumol/l) for 30 min and superfused for 200 min contained [3H]-noradrenaline (183 pmol/g) and [3H]-DOMA (89 pmol/g). The 3H that overflowed into the perfusate between 85 and 90 min consisted mainly of metabolites. Stimulation of the sympathetic nerves through field electrodes increased the overflow of [3H]-noradrenaline into the perfusate threefold without affecting the overflow of metabolites. The increase was much greater (eightfold) in the presence of an alpha-adrenoceptor antagonist (rauwolscine; 0.1 mumol/l), plus inhibitors of uptake1 (desipramine; 0.3 mumol/l) and uptake 2 (corticosterone; 10 mumol/l). The results are interpreted as evidence that in human dental pulp the disposition of exogenous noradrenaline is determined largely by uptake by sympathetic nerves. After uptake, noradrenaline is deaminated by intraneuronal monoamine oxidase to DOPEG and DOMA.(ABSTRACT TRUNCATED AT 250 WORDS)