Orlov S N, Maksimova N V
Laboratory of Physical Chemistry of Biomembranes, School of Biology, Lomonosov Moscow State University, Moscow, 119899, Russia.
Biochemistry (Mosc). 1999 Feb;64(2):127-35.
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.
尽管环核苷酸是亲水性化合物,但在腺苷酸环化酶激活过程中,细胞外cAMP(cAMPo)会迅速积累。本文综述了cAMP通过质膜运输的动力学特性及其生理意义。cAMP的流入和流出通过不同的载体进行。在生理浓度的cAMPo下,cAMP的流入对环核苷酸细胞内含量的调节作用不显著,但在[cAMP]o约为1 mM的实验中,它负责cAMPi的积累。相反,cAMP的高流出速率主要负责在腺苷酸环化酶长期激活过程中[cAMP]i的正常化。本文还探讨了ATP结合盒蛋白(ABC蛋白)可能参与细胞内cAMP流出的情况。在原核生物中,cAMPo是细胞集落形成过程中的信号分子,作用于与GTP结合蛋白相互作用的特殊受体。在脊椎动物中尚未发现此类受体,在大多数情况下,cAMPo的信号功能是通过其被细胞外酶降解,随后激活腺苷受体来介导的。