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Adenosine 3',5'-Monophosphate in Glial Tumor Cells

ALTERATIONS BY 5-BROMODEOXYURIDINE

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

The effect of 5-bromodeoxyuridine (BrdUrd) on the ability of the glial tumor cell line, C-6, to elevate its adenosine 3',5'-monophosphate (cAMP) content in response to norepinephrine has been examined. Increasing concentrations of BrdUrd were found to inhibit the norepinephrine response progressively, with a maximal inhibition of approximately 80%. No effect of BrdUrd was seen on basal cAMP levels. Analysis of individual enzymes demonstrated that BrdUrd increased the cAMP phosphodiesterase activities but had no effect on the adenylate cyclase or its sensitivity to norepinephrine. In addition, BrdUrd caused a change in the shape of the cells. The effect on shape also occurred in confluent cells, whereas the effect on the norepinephrine response required dividing cells, suggesting that incorporation of the BrdUrd into DNA was required.

N⁶, O²'-Dibutyryl adenosine 3',5'-monophosphate also increased the cAMP phosphodiesterase activities of the cells, and caused a similar change in their morphology.

Although BrdUrd had no effect on the adenylate cyclase, variations in the culture conditions were found to have a large effect on the enzyme's norepinephrine sensitivity. Following subculturing, there was little elevation of cAMP in response to norepinephrine until after the cells began to enter the stationary growth phase. Phosphodiesterase activity was found to remain constant throughout this period. The results suggest that cell-to-cell contact may regulate certain cellular functions.

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