Molecular Pharmacology, Vol 10, 162-174, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Norepinephrine-Sensitive Properties of C-6 Astrocytoma Cells

¹ Department of Pharmacology, College of Medicine and Dentistry of New Jersey, Rutgers Medical School, Piscataway, New Jersey 08854

C-6 astrocytoma cells respond to 0.1 mM norepinephrine by a greater than 200-fold elevation of adenosine cyclic 3', 5'-monophosphate (cAMP) and an 80% degradation of glycogen during 20 min of incubation in Ham’s F-10 medium. Evaluation of the time course of these effects indicated that glycogenolysis occurred nonlinearly at a rate of 1-2 nmoles/min/mg of protein; cAMP was maximally elevated after 5 min of incubation and remained so for the 30-min experiment. Norepinephrine induced transformation of glycogen phosphorylase to the 3'-AMP-independent or a form during the first 30 sec of incubation. At the time when phosphorylase a formation had begun, 5 sec after norepinephrine addition, cAMP was elevated only 10-fold. During a 3-hr treatment of cells with norepinephrine, cAMP and glycogen concentrations returned to nearly control concentrations; yet incubation fluid retained sufficient norepinephrine to elevate cAMP as before in fresh samples of cells. Treatment of C-6 cells with norepinephrine for 3 hr followed by 1 hr of incubation without hormone largely suppressed the effect of a second norepinephrine treatment on cAMP concentration, but glycogenolysis occurred as before. 1-Methyl-3-isobutylxanthine, an inhibitor of cAMP phosphodiesterase, partially overcame the suppression of the norepinephrine effects when added with norepinephrine. It is concluded that C-6 astrocytoma cells contain a norepinephrine-activated system of enzymes for degrading glycogen and that norepinephrine treatment modifies the response of the cells to subsequent exposure to this neurohormone.

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