RELEASE OF [³H]NORADRENALINE AND [³H]DOPAMINE FROM FIELD STIMULATED CEREBRAL CORTEX SLICES EFFECT OF TYROSINE HYDROXYLASE AND DOPAMINE‐β‐HYDROXYLASE INHIBITION.¹

Abstract

Abstract— Rat cerebral cortex slices were incubated in vitro with [ 3 H]dopamine (DA) or [ 3 H]noradrenaline (NA) (10 −7 M), superfused by fresh buffer and stimulated by an electric field. The stimulation‐induced overflow of [ 3 H]DA and [ 3 H]NA was determined. In slices from untreated rats about 16 ng [ 3 H]NA/g tissue was formed from [ 3 H]DA, corresponding to about 5 per cent of the endogenous NA concentration. Stimulation markedly enhanced the overflow of [ 3 H]NA. The [ 3 H]NA newly formed from [ 3 H]DA was overflowing to a greater extent than [ 3 H]NA previously taken up from the incubation medium, indicating a preferential release of newly synthesized transmitter. The stimulation‐induced overflow of [ 3 H]DA and [ 3 H]NA was increased in slices of rats pretreated with a tyrosine hydroxylase inhibitor (H44/68). It seems that depletion of the endogenous NA stores of central NA neurons by tyrosine hydroxylase inhibition makes the [ 3 H]cate‐cholamines more available for release. Pretreatment of the rats with the DA‐β‐hydroxylase inhibitors FLA63 or FLA69 considerably diminished the formation of [ 3 H]NA from [ 3 H]DA. Stimulation markedly enhanced the overflow of [ 3 H]DA indicating that DA can act as a ‘false transmitter’ in central NA neurons after DA‐β‐hydroxylase inhibition.