Relationship between dopamine content and its secretion in PC12 cells as a function of cell growth

The PC12 cell line derived from a rat adrenal medullary tumor is known to synthesize dopamine and to release it in response to cholinergic agonists or depolarizing agents. In this report, we have studied the relationship between dopamine biosynthesis and its stimulus-induced secretion in PC12 cells as a function of cell growth. The endogenous dopamine content was found to depend on cell growth, and reached a maximum in the stationary phase. This increase was associated both with an increase in the specific activity of tyrosine 3-monooxygenase, and with an increase of DOPA-decarboxylase in the cells. On the other hand, the maximal release of dopamine occurred in the late exponential phase before the endogenous dopamine was maximally synthesized in the cells. Moreover, the uptake of 45Ca2+ stimulated with either carbamylcholine or high K+ was also regulated by cell division: the maximal uptake took place in the same period of culture in which the maximal release of dopamine was observed. Thus, this report offers new evidence that the biosynthesis and secretion of dopamine are separately regulated in PC12 cells.