Regulation of muscarinic stimulation of norepinephrine release and PI hydrolysis during cell growth in PC12 cells

We have studied the relationships of cell growth to muscarinic stimulation of norepinephrine release and phosphoinositide hydrolysis in the rat pheochromocytoma PC12 cells. The ability of these cells to release norepinephrine in response to muscarinic agonists was maximal during the early phase of exponential growth, and then rapidly decreased to undetectable levels as the cells approached stationary phase. In contrast, muscarinic stimulation of phosphoinositide hydrolysis was low in the early exponential phase of growth, increased to a maximum during late exponential growth and then dramatically dropped in the stationary phase. The number of muscarinic receptors, as measured by antagonist-binding studies, also varied during cell growth with maximal levels at days 2 and 8, corresponding to the maxima in muscarinic-stimulated norepinephrine release and phosphoinositide hydrolysis, respectively.