Learn More
We have developed a rapid, yeast-based, two-step assay to screen for antiprion drugs. The method allowed us to identify several compounds effective against budding yeast prions responsible for the [PSI+] and [URE3] phenotypes. These inhibitors include the kastellpaolitines, a new class of compounds, and two previously known molecules, phenanthridine and(More)
BACKGROUND AND PURPOSE TRPM4 and TRPM5 are calcium-activated non-selective cation channels with almost identical characteristics. TRPM4 is detected in several tissues including heart, kidney, brainstem, cerebral artery and immune system whereas TRPM5 expression is more restricted. Determination of their roles in physiological processes requires specific(More)
Cyclin-dependent kinases (CDKs) regulate the cell cycle, apoptosis, neuronal functions, transcription, and exocytosis. The observation of CDK deregulations in various pathological situations suggests that CDK inhibitors may have a therapeutic value. In this article, we report on the identification of 6-phenyl[5H]pyrrolo[2,3-b]pyrazines (aloisines) as a(More)
Chloride channels play an important role in the physiology and pathophysiology of epithelia, but their pharmacology is still poorly developed. We have chemically synthesized a series of substituted benzo[c]quinolizinium (MPB) compounds. Among them, 6-hydroxy-7-chlorobenzo[c]quinolizinium (MPB-27) and 6-hydroxy-10-chlorobenzo[c]quinolizinium (MPB-07), which(More)
BACKGROUND Physiologically, salivary secretion is controlled by cholinergic and adrenergic pathways but the role of ionic channels in this process is not yet clearly understood. In cystic fibrosis (CF), most exocrine glands failed to response to beta-adrenergic agonists. METHODS To determine the implication of CFTR in this process, we measured in vivo the(More)
Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered(More)
Analogues of bromo-levamisole and guanidine derivatives including cimetidine are examined in vitro in order to investigate their comparative inhibition, towards alkaline phosphatase (ALP) from human liver and diamine-oxidase (DAO) from human placenta. Bromo-levamisole, considered as a potent selective uncompetitive inhibitor of ALP (Ki, 2.8.10(-6) M at pH(More)
A number of genetic diseases, including cystic fibrosis, have been identified as disorders of protein trafficking associated with retention of mutant protein within the endoplasmic reticulum. In the presence of the benzo(c)quinolizinium drugs, MPB-07 and its congener MPB-91, we show the activation of cystic fibrosis transmembrane conductance regulator(More)
BACKGROUND The airway functions are profoundly affected in many diseases including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). CF the most common lethal autosomal recessive genetic disease is caused by mutations of the CFTR gene, which normally encodes a multifunctional and integral membrane protein, the CF transmembrane(More)
1. This study compares the effect of three chemically unrelated cystic fibrosis transmembrane conductance regulator (CFTR) activators on epithelial cell monolayers expressing the G551D-CFTR mutant. 2. We measured Cl(-) transport as the amplitude of short-circuit current in response to the membrane permeable cAMP analogue(More)