Cyclic guanosine 3',5' monophosphate mediates the inhibitory effect of atrial natriuretic factor in adrenergic, neuronal pheochromocytoma cells

This study tests the hypothesis that atrial natriuretic factor (ANF) inhibits catecholamine release from rat pheochromocytoma cells by increasing levels of intracellular cyclic GMP (cGMP). Rat differentiated pheochromocytoma cells are a model of adrenergic nerves and allow the exploration of the effects of various hormones, autacoids, drugs and neuromodulators on adrenergic neurotransmission in cell culture. Synthetic rat ANF (99-126) inhibited K⁺-induced norepinephrine and dopamine release, as measured by high-performance liquid chromatography, in a concentration-dependent manner over the concentration range of 10^-11 to 10^-8 M. ANF stimulated intracellular cGMP accumulation, as measured by specific radioimmunoassay, in a concentration-dependent manner over the same concentration range. The cGMP analog, N²-2'-O-dibutyryl cGMP also inhibited K⁺-induced norepinephrine and dopamine release in a concentration-dependent manner. The results of this study are consistent with the hypothesis that ANF acts as an inhibitory neuromodulator in adrenergic nerves via the second messenger, cGMP.