Cellular mechanisms of action of atrial natriuretic factor.
Atrial natriuretic factor (ANF) interacts with its target cells through specific receptors. This interaction induces, in most cell types, the activation of particulate guanylate cyclase and decreased Calcium mobilisation. In addition, ANF also decreases adenylate cyclase activity in some tissues. Activation of particulate guanylate cyclase, and additionally inhibition of adenylate cyclase, appear to initiate the cellular responses to circulating ANF. The activation of particulate guanylate cyclase is tissue-specific, immediate and can be demonstrated also on the solubilized enzyme. The ANF receptor appears to be tightly coupled to particulate guanylate cyclase. The increased formation of cyclic GMP induces cGMP-dependent protein phosphorylation in target cells. In addition, cyclic GMP inhibits Calcium mobilisation in several tissues. This may explain observations of inhibition of Calcium mobilisation after ANF. Cyclic GMP is not only degraded by phosphodiesterase, but is also extruded from target cells. As a consequence of cGMP extrusion, ANF increases the levels of cyclic GMP in plasma and urine in animals and man. Cyclic GMP is also increased in various disease states, in which ANF is increased. In contrast, cyclic AMP plasma levels are unaltered after ANF elevations. At present, the exact mechanisms, by which cellular functions are altered by ANF are still incompletely understood. It is anticipated, that the close correlation between the cyclic GMP system and effects of ANF in various target tissues is a key finding that will help elucidate the exact mechanisms of ANF action.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology / Q000502:physiology*; D001696:Biomechanical Phenomena; D002118:Calcium / Q000037:antagonists & inhibitors; D002468:Cell Physiological Phenomena; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism
D000067956:Adenylyl Cyclase Inhibitors; D011506:Proteins; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium