Extraneuronal uptake of noradrenaline in rabbit dental pulp: evidence of identity with uptake1

Abstract

The extraneuronal removal and disposition of noradrenaline in rabbit dental pulp was examined in view of earlier evidence that the tissue possessed an extraneuronal uptake process resembling neuronal uptake1. Pulp, which had been depleted of sympathetic nerves by homolateral superior cervical ganglionectomy, was incubated in vitro with 3H-noradrenaline in low concentrations (0.025 or 0.18 mumol/l). When the metabolising enzymes (monoamine oxidase, catechol-O-methyl transferase) were active, 3H retention by the denervated pulp, as indicated by the 3H content after the tissue had been washed for 30 min following incubation with 3H-noradrenaline, was less than 3% of that of the innervated pulp. When the enzymes were inhibited, retention rose to approximately 30% of that of the innervated pulp. Analysis of the time course of the 3H efflux indicated that the 3H-noradrenaline in the denervated pulp had accumulated in a single compartment characterised by a t1/2 for efflux of several hours. Accumulation did not occur under Na(+)-free conditions, and was inhibited by desipramine (IC50 less than 0.03 mumol/l) and by substrates of neuronal uptake1. Mean IC50 values of the latter were very similar to those for inhibition of neuronal uptake1 and comprised (in mumol/l): (+)amphetamine (0.29), dopamine (0.31), tyramine (0.39), (-)noradrenaline (0.70), (-)adrenaline (1.50), 5-hydroxytryptamine (20) and bretylium (35). Uptake2 inhibitors were less active (O-methyl isoprenaline, IC50 = 60 mumol/l) than uptake1 inhibitors, or were without inhibitory effects at the concentrations tested (hydrocortisone, 210 mumol/l; 2-methoxy oestrone, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)