TY - JOUR T1 - Cyclic guanosine 3',5' monophosphate mediates the inhibitory effect of atrial natriuretic factor in adrenergic, neuronal pheochromocytoma cells. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 428 LP - 432 VL - 250 IS - 2 AU - J G Drewett AU - R J Ziegler AU - G R Marchand AU - G J Trachte Y1 - 1989/08/01 UR - http://jpet.aspetjournals.org/content/250/2/428.abstract N2 - 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. ER -