Current Pharmaceutical Design - Volume 18, Issue 2, 2012

The cells need to respond rapidly and with high fidelity to their changing environment, having in their disposition a low abundance of signaling components in cell membranes. To achieve this task, plasticity is needed. Growing evidence has shown that structural plasticity provides the cell with the required diversity. Seven-transmembrane receptors (7TMRs), also called G protein-coupled receptors (GPCRs) are the most dive Read More

G protein receptor kinase 2 (GRK2) has been for years mainly considered the negative regulator of the cardiac β adrenergic signaling. However GRK2 is a ubiquitous molecule and its kinase activity and scaffold properties brought to several investigations which have evidenced its involvement in pathophysiology of extra-cardiac diseases. Later discoveries, moreover, indicated that this molecule is also able to influence other pat Read More

Cell surface G protein-coupled receptors (GPCRs) drive numerous signaling pathways involved in the regulation of a broad range of physiologic processes. Today, they represent the largest target for modern drugs development with potential application in all clinical fields. Recently, the concept of “ligand-directed trafficking” has led to a conceptual revolution in pharmacological theory, thus opening new avenues for dru Read More

Components of 7TMR signaling machinery once considered as rigid, fixed and inflexible entities, operating in a onedimensional way, homogeneous spatially and temporally, are now proved to be structurally plastic, flexible and dynamic in space and time. 7TMRs are thought to exist as ensembles of multiple, inter-convertible, pre-existing conformations and this conformational diversity provides a structural plasticity and Read More

The Protease-Activated Receptors ( PARs ) are G-protein-coupled receptors ( GPCRs ) characterized by a unique mechanism of activation. They carry built in their extended N-terminal structure their own activating agonist, in the form of a cryptic tethered ligand , unmasked by an irreversible proteolytic cleavage. Besides, PARs display several other particular properties, that converge and create interacting and intertwined lay Read More

G-protein coupled receptors (GPCRs) comprise the largest family of proteins in our body, which have many important physiological functions and are implicated in the pathophysiology of many serious diseases. GPCRs therefore are significant targets in pharmaceutical research. GPCRs share the common architecture of seven plasma membrane-spanning segments connected to each other with three extracellular and three in Read More

Despite significant advances in pharmacological and clinical treatment, heart failure (HF) remains the number one killer disease in the western world. HF is a chronic and progressive clinical syndrome mainly characterized by reduction in left ventricular ejection fraction and adverse remodeling of the myocardium. One of its hallmark molecular abnormalities is elevation of cardiac G protein-coupled receptor (GPCR) ki Read More

Heptahelical, G protein-coupled or seven transmembrane-spanning receptors, such as the β-adrenergic and the angiotensin II type 1 receptors, are the most diverse and therapeutically important family of receptors in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signal Read More

It is with great sadness that we record here the premature death of Herve Paris, who died at his home in Toulouse, in January 23, 2010. With his death, molecular pharmacology research of GPCRs has lost one of its creative, productive and most consistent supporters. He studied in the University of Paul Sabatier, Toulouse III, France and at the University of Miami, USA. With this basic background he served at INSERM (Ins Read More

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta. To date, although a bulk of evidences suggest that the etiology of PD is multifactorial, none of the mechanisms yet proposed have been considered conclusive. Activated glia seem to play a critical role in the degeneration of nigral dopaminergic neurons in PD, by Read More

Recent years have broadened the spectrum of therapeutic strategies and specific agents for treatment of multiple sclerosis (MS). While immune-modulating drugs remain the first-line agents for MS predominantly due to their benign safety profile, our growing understanding of key processes in initiation and progression of MS has pioneered development of new agents with specific targets. One concept of these novel drugs is t Read More

Enkephalins play a great role in management of pain, blood pressure, hypertension and cardiovascular diseases. Enkephalins are short-lived molecules being rapidly hydrolyzed following their synaptic release by enkephalin degrading enzymes. The inhibitors of enkephalin degrading enzymes are able to prolong the duration of action of enkephalins. This review will focus on the inhibitors of enkephalin degrading enzy Read More