METABOLISM OF [H-3] NORADRENALINE IN HUMAN DENTAL-PULP IN-VITRO

Slices of pulp from human maxillary and mandibular molar and promolar teeth were incubated with [H-3]-noradrenaline (0.2 mu mol/l) for 30 mi n after which the [H-3]-noradrenaline and [H-3]-metabolites in the tis sue and medium were assayed by column chromatography. The deaminated m etabolites 3,4-dihydroxy phenyl glycol (DOPEG) and 3,4-dihydroxy mande lic acid (DOMA) constituted 81% of the metabolites formed. Cocaine, an inhibitor of uptake,, decreased the formation of DOPEG and DOMA as we ll as the accumulation of [H-3]-noradrenaline. In contrast to findings in rabbit pulp, when the disposition of exogenous noradrenaline in hu man pulp was examined by monoamine fluorescence histochemistry there w as no evidence of extraneuronal accumulation of noradrenaline by conne ctive tissue cells. In further experiments, pulp that had been incubat ed in [H-3]-noradrenaline (0.6 mu mol/l) for 30 min and superfused for 200 min contained [H-3]-noradrenaline (183 pmol/g) and [H-3]-DOMA (89 pmol/g). The H-3 that overflowed into the perfusate between 85 and 90 min consisted mainly of metabolites. Stimulation of the sympathetic n erves through field electrodes increased the overflow of [H-3]-noradre naline 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 mu mol/l), plus inhibitors of uptake, (desipramine; 0.3 mu mol/l) and uptake, (cortic osterone; 0.1 mu mol/l). The results are interpreted as evidence that in human dental pulp the disposition of exogenous noradrenaline is det ermined largely by uptake by sympathetic nerves. After uptake, noradre naline is deaminated by intraneuronal monoamine oxidase to DOPEG and D OMA. The firm retention of noradrenaline by the pulp and its release b y nerve stimulation implies that the amine is stored in intraneuronal vesicles.