Efflux of cyclic adenosine monophosphate from cells: mechanisms and physiological implications

Although cyclic nucleotides are hydrophilic compounds, extracellular cAMP (cAMPo) rapidly accumulates during the activation of adenylate cyclase. This review considers the kinetic characteristics of cAMP transport through the plasma membrane and its physiological implications. The influx and efflux of cAMP occur via different carriers. At physiological concentrations of cAMPo, the influx of cAMP does not significantly contribute to regulation of the intracellular content of the cyclic nucleotide, but it is responsible for the accumulation of cAMPi in experiments at [cAMP]o approximately 1 mM. In contrast, the high rate of cAMP efflux is mainly responsible for normalization of [cAMP]i during long-term activation of adenylate cyclase. The possible involvement of ATP-binding cassette proteins (ABC proteins) in the efflux of cAMP from the cell is considered. In procaryotes cAMPo is a signal molecule during the generation of cell colonies, acting on special receptors that interact with GTP-binding proteins. Such receptors have not been found in vertebrates, and in most cases the signal functions of cAMPo are mediated by its degradation by extracellular enzymes with subsequent activation of adenosine receptors.