Cyclic GMP Phosphodiesterases and Regulation of Smooth Muscle Function

摘要: Cyclic GMP (cGMP) made in response to atrial natriuretic peptide (ANP) or nitric oxide (NO) is an important regulator of short-term changes smooth muscle tone and longer-term responses chronic drug treatment proliferative signals. The ability cells (SMCs) utilize different combinations phosphodiesterase (PDE) isozymes allows cGMP mediate these multiple processes. For example, PDE5 as a major cGMP-hydrolyzing PDE effectively controls the development relaxation. In order for contraction occur, activated falls. Conversely, blockade activity relaxation cycle be prolonged enhanced. A recently shown direct activation by binding GAF domain suggests that this regulatory site might target new development. calcium surge associated with vasoconstrictor initiated also activates calcium/calmodulin-dependent (PDE1A). Together, PDE1A lower sufficiently allow contraction. Longer term, both mRNA are induced stimulation guanylyl cyclase. This induction cause tolerance develops NO-releasing drugs. Finally, high levels cAMP act brake attenuate SMCs many mitogens. After vessel damage, SMC proliferation must decreased. humans, decrease caused large part another Ca2+/calmodulin-dependent (PDE1C) released start.