REVIEW: Efflux of Cyclic Adenosine Monophosphate from Cells: Mechanisms and Physiological Implications

S. N. Orlov^1,2 and N. V. Maksimova^1*

¹Laboratory of Physical Chemistry of Biomembranes, School of Biology, Lomonosov Moscow State University, Moscow, 119899 Russia: fax: (095) 939-2260; E-mail: orlovs@ere.umontreal.ca

²Laboratory of Molecular Medicine, Medical School Research Center, University of Montreal, Montreal, Canada

^* To whom correspondence should be addressed.

Received June 25, 1998; Revision received August 5, 1998

---

Although cyclic nucleotides are hydrophilic compounds, extracellular cAMP (cAMP_o) 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 cAMP_o, 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 cAMP_i in experiments at [cAMP]_o ~ 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 cAMP_o 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 cAMP_o are mediated by its degradation by extracellular enzymes with subsequent activation of adenosine receptors.

---

KEY WORDS: cAMP, transport, physiological implications

---