Regulation of cAMP by phosphodiesterases in erythrocytes.
The erythrocyte, a cell responsible for carrying and delivering oxygen in the body, has often been regarded as simply a vehicle for the circulation of hemoglobin. However, it has become evident that this cell also participates in the regulation of vascular caliber in the microcirculation via release of the potent vasodilator, adenosine triphosphate (ATP). The regulated release of ATP from erythrocytes occurs via a defined signaling pathway and requires increases in cyclic 3',5'- adenosine monophosphate (cAMP). It is well recognized that cAMP is a critical second messenger in diverse signaling pathways. In all cells increases in cAMP are localized and regulated by the activity of phosphodiesterases (PDEs). In erythrocytes activation of either beta adrenergic receptors (beta(2)AR) or the prostacyclin receptor (IPR) results in increases in cAMP and ATP release. Receptor-mediated increases in cAMP are tightly regulated by distinct PDEs associated with each signaling pathway as shown by the finding that selective inhibitors of the PDEs localized to each pathway potentiate both increases in cAMP and ATP release. Here we review the profile of PDEs identified in erythrocytes, their association with specific signaling pathways and their role in the regulation of ATP release from these cells. Understanding the contribution of PDEs to the control of ATP release from erythrocytes identifies this cell as a potential target for the development of drugs for the treatment of vascular disease.
Adderley
Shaquria P
SP
Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, USA. sadderle@slu.edu
Sprague
Randy S
RS
Stephenson
Alan H
AH
Hanson
Madelyn S
MS
D000818:Animals; D002451:Cell Compartmentation; D000242:Cyclic AMP / Q000097:blood* / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000097:blood / Q000378:metabolism; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000097:blood / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000097:blood / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000097:blood / Q000378:metabolism; D004912:Erythrocytes / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D010727:Phosphoric Diester Hydrolases / Q000097:blood* / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction
D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C517275:PDE2A protein, human; C517287:PDE3A protein, human; C517291:PDE3B protein, human; C517355:PDE4A protein, human