Abstract

Stimulation of the hypogastric nerve to the guinea pig vas deferens in vitro in the presence of a normal extracellular calcium concentration produced a proportional release of dopamine β-hydroxylase (EC 1.14.2.1) and norepinephrine. Both dibutyryl cyclic AMP (0.1 mM) and theophylline (1 mM) enhanced stimulation-induced release of dopamine β-hydroxylase and norepinephrine, with dibutyryl cyclic AMP also increasing spontaneous release. In a calcium-free medium the stimulation-induced release of dopamine β-hydroxylase and norepinephrine was completely blocked. However, stimulation-induced release did occur when either dibutyryl cyclic AMP (0.1 mM) or theophylline (1 mM) was added to the calcium-free medium. As in the medium containing a normal calcium concentration, dibutyryl cyclic AMP enhanced spontaneous release of dopamine β-hydroxylase and norepinephrine. The ratio of dopamine β-hydroxylase to norepinephrine released was identical whether release was spontaneous or electrically induced and whether or not dibutyryl cyclic AMP or theophylline was present. Thus dibutyryl cyclic AMP and theophylline do not require extracellular calcium to cause the release of neurotransmitter by exocytosis at sympathetic nerve endings. These results suggest that cyclic 3',5'-AMP may have a role in release, acting either in parallel with calcium or indirectly by mobilizing intracellular, bound calcium.