Export of cyclic AMP from avian red cells. Independence from major membrane transporters and specific inhibition by prostaglandin A.
Prostaglandin A1 (PGA1) inhibits energy-dependent cyclic AMP export by pigeon red cells [Brunton and Mayer, J. Biol. Chem. 254:9714 (1979)]. To assess the specificity of this action, we observed the effect of 10 microM PGA1 (a concentration that inhibits cyclic AMP efflux greater than 95%) on a variety of membrane-protein-mediated processes that we could readily characterize and quantify in the pigeon red cell. Included in this study were isoproterenol-sensitive cyclic AMP production, ouabain-inhibitable 86Rb+ influx, furosemide-sensitive NaCl-KCl symport, 4-acetamido-4'-isothiocyano-2, 2'-disulfonic stilbene (SITS)-sensitive sulfate exchange, Na+-dependent alpha-aminoisobutyrate influx, and glucose and adenosine uptake. Remarkably, none of these membrane activities is significantly affected by PGA1. Furthermore, SITS, nitrobenzylthioinosine, cytochalasin B, and Na+-free extracellular medium (inhibitors of band 3, the nucleoside transporter, the hexose transporter, and amino acid uptake, respectively), failed to inhibit cyclic AMP export by pigeon red cells. On the basis of this data, we conclude that PGA1 does not act via a generalized alteration of a basic property at the plasma membrane, such as its fluidity; rather, PGA1 acts specifically to inhibit cyclic AMP extrusion. The data also imply that a transporter not relying on the Na+ gradient and distinct from transporters of cations, anions, amino acids, sugars, and nucleosides mediates cyclic AMP export.
Heasley
L E
LE
Azari
J
J
Brunton
L L
LL
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D010856:Columbidae; D000242:Cyclic AMP / Q000097:blood*; D002373:Cyclic AMP Receptor Protein; D003571:Cytochalasin B / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000494:pharmacology; D011190:Potassium Cyanide / Q000494:pharmacology; D011454:Prostaglandins A / Q000494:pharmacology*; D012413:Rubidium / Q000097:blood; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology
D001786:Blood Glucose; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D011454:Prostaglandins A; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D003571:Cytochalasin B; D013868:Thioinosine; D010042:Ouabain; D000242:Cyclic AMP; C001789:4-nitrobenzylthioinosine; D012413:Rubidium; D011190:Potassium Cyanide; C100573:prostaglandin A1