PDEs superfamily

Today 11 members of the human PDE superfamily are known, all of which are class I phosphodiesterases and all of which are intracellular or membrane-bound enzymes. Several of the isoenzymes are encoded by more than one gene which, in combination with the presence of different splice variants, brings the number of different PDE proteins to well over 50. The different isoenzymes are characterized according to their substrate specificity, sequence homology, kinetic properties, and sensitivity to certain known PDE inhibitors. Table 9.1 shows these properties together with the predominant tissue expression of the various PDEs. 

Lugnier C (2006) Cyclic nucleotide phosphodiesterase (PDE) superfamily a new target for the development of specific therapeutic agents. Pharmacol Ther 109 366-398... 

The family of heterotrimeric G proteins is involved in transmembrane signaling in the nervous system, with certain exceptions. The exceptions are instances of synaptic transmission mediated via receptors that contain intrinsic enzymatic activity, such as tyrosine kinase or guanylyl cyclase, or via receptors that form ion channels (see Ch. 10). Heterotrimeric G proteins were first identified, named and characterized by Alfred Gilman, Martin Rodbell and others close to 20 years ago. They consist of three distinct subunits, a, (3 and y. These proteins couple the activation of diverse types of plasmalemma receptor to a variety of intracellular processes. In fact, most types of neurotransmitter and peptide hormone receptor, as well as many cytokine and chemokine receptors, fall into a superfamily of structurally related molecules, termed G-protein-coupled receptors. These receptors are named for the role of G proteins in mediating the varied biological effects of the receptors (see Ch. 10). Consequently, numerous effector proteins are influenced by these heterotrimeric G proteins ion channels adenylyl cyclase phosphodiesterase (PDE) phosphoinositide-specific phospholipase C (PI-PLC), which catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) and phospholipase A2 (PLA2), which catalyzes the hydrolysis of membrane phospholipids to yield arachidonic acid. In addition, these G proteins have been implicated in... 

PDE belongs to a superfamily of enzymes that regulate cell function by maintaining cyclic nucleotide levels. There are cAMP-specific PDEs (PDE4, PDE7, and PDE8),... 

Cyclic AMP (cAMP) is an important intracellular mediator regulating the activation of inflammatory cells. Particularly important with respect to asthma, cAMP also plays a role in regulating airway and vascular smooth muscle contractibility, inflammatory cell proliferation, and pulmonary neuronal responsiveness. Cyclic phosphodiesterases (PDEs) comprise a protein superfamily, whose function is to inactivate cyclic AMP and cyclic GMP. The fact that certain PDE inhibitors suppress immune cell functions in vitro and pulmonary inflammation in vivo may represent an opportunity for the development of novel anti-inflammatory drugs. 

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