The Quantitative Relationship between Intracellular Concentration and Egress of Cyclic AMP from Cultured Cells

Abstract

To test the hypothesis that cyclic AMP egress was a function of intracellular concentration, the relationship between those quantities was investigated. It was found that there was a linear relationship between intracellular concentration and the rate of egress of the nucleotide in the four cultured cell lines tested (WI-38, VA13, MRC-5, and IMR-90). The ability to relate egress to intracellular concentration for these cells allowed a quantitative approach to several long-standing questions on the role and mechanism of cyclic AMP egress. Thus, the effects of 3-isobutyl-1-methylxanthine and meclofenamate on egress were determined. In addition, this approach has been used to show that egress is not dependent either on free diffusion or on a passive carrier mechanism. It is, therefore, presumably energy-dependent. Finally, in conjunction with previously published data, it was shown that egress of cyclic AMP is not a major factor in the control of intracellular accumulation of the nucleotide in these cells. Egress accounted for no more than 15.5% of the total turnover of cyclic AMP in WI-38 cells and 18% in VA13 cells.