The effect of cyclic nucleotides on the release of 3H-dopamine from rat striatal slices

Slices (1.0 mm thick and 0.4 cm in diameter) obtained from rat neostriatum were preincubated with 3H-dopamine (3H-DA; 0.8 mugM) for 30 minutes and then superfused at a rate of 1.0 ml/min in glass chambers (volume, 2 ml) for varying lenghts of time prior to electrical stimulation. Superfusate effluents were continuously collected and analyzed for 3H-DA and 3H-metabolites by liquid scintillation spectrometry after separation by alumina and Dowex 50 column chromatography. 3H-DA represented only a small proportion of the spontaneous overflow of radioactivity (9.8%) but represented the largest portion recovered in the tissue (55%). After electrical stimulation of the slices (biphasic square-wave pulses, 50 pulses/sec; 1.1-msec duration; supramaximal voltage), there was a marked increase in 3H-DA and all 3H-fractions. The percent increase of 3H-DA, 3H-O-methylated + 3H-O-methylated deaminated, 3H-dihydroxyphenylacetic acid and 3H-dihydroxylphenylethanol was 549, 232, 215 AND 246%, respectively. The addition to the superfusion medium of dibutyryl adenosine 3:5-monophosphate (DBcAMP) in the presence or absence of phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, 0.5 mM, or aminophylline, 5 mM) and cyclic adenosine monophosphoric acid in the presence but not the absence of the phosphodiesterase inhibitors potentiated the electrically induced release of 3H-DA. Neither cyclic nucleotide had any effect on the spontaneous overflow of 3H-DA or metabolites, the metabolism of 3H-DA or the uptake of 3H-DA into dopaminergic neurons. Guano sine 3:5-monophosphate was without effect on the electrically induced release of 3H-DA. The ED50 for the DBcAMP potentiation of hte electrically induced release of 3H-DA was 6 mugM. These results extend to the central nervous system the possibility that adenosine 3-5-monophosphate may play a role in the regulation or modulation of monoaminergic synaptic transmission.