The P2X7 receptor is an adenosine triphosphate (ATP)-gated cation channel that is expressed by several cells of the immune system. P2X7 is best known for its proinflammatory role in promoting inflammasome formation and release of mature interleukin (IL)-1β by innate immune cells. Mounting evidence indicates that P2X7 is also an important regulatory receptor of murine and human T cell functions....

BACKGROUND Chronic lymphocytic leukaemia (CLL) has a familial incidence nearly three times higher than expected for the general population and one predisposing factor might be an inherited failure of mechanisms involved in apoptosis of lymphocytes. Our aim was to ascertain whether or not a defect in a proapoptotic pathway, caused by a single nucleotide polymorphism that results in loss-of-funct...

background: radioprotective capability of histamine h2 receptor antagonists have been shown in several in vivo studies mainly using animal models. however, to verify the effectiveness of these agents in clinical applications, studies should be performed on human cells. in the present study radioprotective properties of these agents was examined in vitro on human lymphocytes using metaphase anal...

The importance in vivo of P2X7 receptors in control of virulent Mycobacterium tuberculosis was examined in a low-dose aerosol infection mouse model. P2X7(-/-) mice controlled infection in lungs as well as wild-type mice, suggesting that the P2X7 receptor is not required for control of pulmonary M. tuberculosis infection.

Pannexin 1 forms a large membrane channel that, based on its biophysical properties and its expression pattern, is a prime candidate to represent an ATP release channel. Pannexin 1 channel activity is potentially deleterious for cells as indicated by its involvement in the P2X7 death complex. Here we describe a negative feedback loop controlling pannexin 1 channel activity. ATP, permeant to pan...

Cannabinoid type-1 (CB1) receptor antagonists wereamong the most promising drug targets in the last decade. Theyhave been explored and found to be effective as therapeutic agentsfor obesity and related cardiometabolic problems, including e.g.dyslipidaemias, diabetes, and metabolic syndrome. However, theuse of rimonabant, the first marketed CB1 receptor antagonist, hasbee...

....................................................................................................................... ii ACKNOWLEDGMENTS ................................................................................................. iv TABLE OF CONTENTS ................................................................................................... vi LIST OF ABBREVIATIONS .................

Among the family of P2X ATP-gated cation channels, the P2X7 receptor is a homomeric subtype highly expressed in immune cells of the monocyte-macrophage lineage. We report here that the WC167-168AA mutation in the ectodomain of P2X7 produced nonfunctional subunits with strong dominant-negative effect on wild-type P2X7 receptors (77% inhibition with cotransfection of wild-type and mutant DNA at a...