The rod photoreceptor phosphodiesterase (PDE) is unique among all known vertebrate PDE families for several reasons. It is a catalytic heterodimer (alphabeta); it is directly activated by a G-protein, transducin; and its active sites are regulated by inhibitory gamma subunits. Rod PDE binds cGMP at two noncatalytic sites on the alphabeta dimer, but their function is unclear. We show that transd...

Recent studies have demonstrated that functionally discrete pools of phosphodiesterase (PDE) activity regulate distinct cellular functions. While the importance of localized pools of enzyme activity has become apparent, few studies have estimated enzyme activity within discrete subcellular compartments. Here we present an approach to estimate near-membrane PDE activity. First, total PDE activit...

The binding of cGMP to the noncatalytic sites on two isoforms of the phosphodiesterase (PDE) from mammalian rod outer segments has been characterized to evaluate their role in regulating PDE during phototransduction. Nonactivated, membrane-associated PDE (PDE-M, alpha beta gamma2) has one exchangeable site for cGMP binding; endogenous cGMP remains nonexchangeable at the second site. Non-activat...

In addition to its emerging immunodulatory properties, theophylline is a bronchodilator and also decreases mean pulmonary arterial pressure in vivo. The mechanism of action of this drug remains controversial; adenosine antagonism, phosphodiesterase (PDE) inhibition and other actions have been advanced to explain its effectiveness in asthma. Cyclic adenosine monophosphate (AMP) and cyclic guanos...

This paper presents a method for interactive design by means of extending the PDE based approach for surface generation. The governing partial differential equation is generalized to arbitrary order allowing complex shapes to be designed as single patch PDE surfaces. Using this technique a designer has the flexibility of creating and manipulating the geometry of shape that satisfying an arbitra...

PURPOSE Cyclic GMP phosphodiesterase (PDE) is the light-regulated effector enzyme of vertebrate rods. Upon photo-activation of rhodopsin followed by activation of transducin/GTP, PDE rapidly hydrolyzes 3', 5'-cyclic GMP (cGMP) to 5'-GMP, which results in closure of cGMP-dependent ion channels and generation of a nerve signal. In the rod photoreceptors, PDE is entirely localized within the rod o...

The gamma-subunit of retinal rod-outer-segment phosphodiesterase (PDE-gamma) is a multifunctional protein which interacts directly with both of the catalytic subunits of PDE (PDE alpha/beta) and the alpha-subunit of the retinal G (guanine-nucleotide-binding)-protein transducin alpha (T alpha). We have previously reported that the PDE gamma binds to T alpha at residue nos. 24-45 [Morrison. Rider...

The aim of this investigation was to prepare, characterize and optimize the aceclofenac proniosomes using central composite design and carry out stability studies. Three independent variables selected were molar ratio of drug to lipid (X1), surfactant loading (X2) and volume of hydration (X3). Based on central composite design, 16 batches of proniosomes were prepared by slurry method and evalua...

The aim of this investigation was to prepare, characterize and optimize the aceclofenac proniosomes using central composite design and carry out stability studies. Three independent variables selected were molar ratio of drug to lipid (X1), surfactant loading (X2) and volume of hydration (X3). Based on central composite design, 16 batches of proniosomes were prepared by slurry method and evalua...