Export of cyclic AMP by mammalian reticulocytes

Suspensions of reticulocyte-enriched red cells produce and extrude cyclic AMP in proportion to their reticulocyte content. When reticulocytes are treated with the beta-adrenergic agonist isoproterenol, up to 3.5 pmoles of cyclic AMP/min/mg protein appear in the extracellular medium. Extruded cyclic AMP can occur against apparent concentration gradients and is inhibited by agents (iodoacetate, dinitrophenol) that deplete cellular ATP, as well as by probenecid and prostaglandin A1. Extrusion of cyclic AMP depends on the availability of intracellular cyclic AMP but is not obligatorily coupled to adenylate cyclase activity: extrusion continues following termination of a pulse of stimulation and exhibits a temperature dependence that differs from that for cyclic AMP production in response to isoproterenol. Erythropoietin affects neither production nor extrusion of cyclic AMP by reticulocytes. In whole blood, cyclic AMP extruded by reticulocytes may be a significant source of plasma cyclic nucleotide.