ADENOSINE 3',5'-CYCLIC-MONOPHOSPHATE STIMULATES DOPAMINE BIOSYNTHESIS IN THE MEDIAN-EMINENCE OF RAT HYPOTHALAMIC SLICES

The regulation of dopamine biosynthesis in tuberoinfundibular dopaminergic (TIDA) neurons by adenosine 3'',5''-cyclic monophosphate (cAMP) was investigated in the present study. Dopamine biosynthesis in TIDA neurons was estimated by the rate of in vitro dihydroxyphenylalanine (DOPA) accumulation in the median eminence of rat hypothalamic slices after incubation with a DOPA decarboxylase inhibitor. Addition of dibutyryl cAMP (db-cAMP) into medium caused an increase in the rate of DOPA accumulation in the median eminence in a dose- and time-dependent manner. 8-Bromo-cAMP also increased the rate of DOPA accumulation in the median eminence and cAMP was less effective than db-cAMP whereas neither adenosine nor sodium butyrate altered the rate of DOPA accumulation. An increase in the concentration of endogenous cAMP achieved by addition into medium of isobutylmethylxanthine, a phosphodiesterase inhibitor, or forskolin, an adenylate cyclase activator, was associated with an increase in the rate of DOPA accumulation in the median eminence. db-cAMP, however, had an almost negligible effect on the secretion of dopamine from the median eminence. The stimulatory effect of db-cAMP on DOPA accumulation in the median eminence was not dependent upon the presence of extracellular Ca2+ and was not blocked by tetrodotoxin. Furthermore, the stimulation of DOPA accumulation in the median eminence induced by db-cAMP was additive with that induced by high potassium depolarization, which was Ca2+-dependent. These results suggest that dopamine biosynthesis in TIDA neurons is regulated by two distinct mechanisms, one of which involves cAMP, and another of which involves Ca2+.