The Mode of Action of Cyclic AMP

Abstract

Cyclic AMP is an adenosine nucleotide with a phosphate group attached in a cyclic arrangement to its ribose moiety at the 3' and 5' carbons. Receptor sites for adrenergic hormones, peptide hormones, and adenosine are found imbedded in the outer layer of the cell's plasma membrane in close association with the enzyme adenyl cyclase. Adenyl cyclase, which catalyzes the synthesis of cyclic AMP from ATP substrate, is located in discrete areas imbedded in the inner layer of the plasma membrane; it is tightly coupled to a transducer protein that possesses a GTP binding site. Adenyl cyclase possesses binding sites for prostaglandins and for calcium and magnesium ions. The adenosine receptor is precoupled to the transducer protein-enzyme complex. Adrenergic receptors, on the other hand, migrate freely in the plasma membrane and activate adenyl cyclase only during a brief collision between the hormone-receptor complex and the transducer-enzyme complex. The cyclic AMP produced as a result of adenyl cyclase activation diffuses into the cell, where it binds to the regulatory subunit of cyclic AMP-dependent protein kinase. The catalytic subunit remaining unbound in the cytoplasm is the active form of protein kinase. Its chief function as a mediator of cyclic AMP stimulation is to phosphorylate various proteins in the cell, thereby altering their function and producing the programmed physiological response of the cell.