Journal
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 53, 2013
Volume 53, Issue -, Pages 231-253Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-010611-134609
Keywords
CFTR; cAMP; efflux; export; MRP4
Categories
Funding
- NCI NIH HHS [P30 CA21745, CA21865, R01 CA194206] Funding Source: Medline
- NIDDK NIH HHS [R01 DK093045, R01 DK080834, R01 DK074996, R01 DK058545] Funding Source: Medline
- NIGMS NIH HHS [2R01 GM60904, R56 GM060904, R01 GM060904] Funding Source: Medline
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Cyclic nucleotides [e.g., cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP)] are ubiquitous second messengers that affect multiple cell functions from maturation of the egg to cell division, growth, differentiation, and death. The concentration of cAMP can be regulated by processes within membrane domains (local regulation) as well as throughout a cell (global regulation). The phosphodiesterases (PDEs) that degrade cAMP have well-known roles in both these processes. It has recently been discovered that ATP-binding cassette (ABC) transporters contribute to both local and global regulation of cAMP. This regulation may require the formation of macromolecular complexes. Some of these transporters are ubiquitously expressed, whereas others are more tissue restricted. Because some PDE inhibitors are also ABC transporter inhibitors, it is conceivable that the therapeutic benefits of their use result from the combined inhibition of both PDEs and ABC transporters. Deciphering the individual contributions of PDEs and ABC transporters to such drug effects may lead to improved therapeutic benefits.
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