The purpose of the present study was (1) to evaluate the functional contribution of nicotinic and muscarinic receptors in the secretion of catecholamines, and (2) to determine whether the signal for exportable catecholamine might also function as a signal for compensatory catecholamine repletion by enhancing the biosynthesis of the released catecholamines in the rat adrenal pheochromocytoma 12 cells. Accordingly, we investigated the secretion of catecholamine and the gene expression and the activity of tyrosine hydroxylase which is the rate limiting enzyme in the synthesis of catecholamine by the treatment of nicotine as a nicotinic receptor agonist and hexamethonium bromide as a nicotinic receptor antagonist to PC-12 cells. In PC-12 cells, 10^(-5) M nicotine caused the significant increase of catecholamine secretion and 4-fold increase in the synthesis of TH mRNA comparing to none treated cells. On the other hand, the results are reverse in 5 × 10^(-5) M hexamethonium-treated cells. Our results, reported here, suggest a possible model for Stimulus-Secretion-Synthesis Coupling Mechanism.