Annual Review of Pharmacology and Toxicology - Volume 46, 2006
Volume 46, 2006
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PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS: How Their Effects on Macrophages Can Lead to the Development of a New Drug Therapy Against Atherosclerosis
Vol. 46 (2006), pp. 1–39More Less▪ Abstract Peroxisome proliferator-activated receptors (PPARs) alpha (α), beta/delta (β/δ), and gamma (γ) are members of the nuclear receptor superfamily, which also includes the estrogen, androgen, and glucocorticoid receptors. Recent evidence suggests that PPARs regulate genes involved in lipid metabolism, glucose homeostasis, and inflammation in various tissues; however, the mechanisms involved are not com Read More
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CYTOCHROME P450 AND XENOBIOTIC RECEPTOR HUMANIZED MICE*
Vol. 46 (2006), pp. 41–64More Less▪ Abstract Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transp Read More
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HUMAN FLAVIN-CONTAINING MONOOXYGENASES
John R. Cashman, and Jun ZhangVol. 46 (2006), pp. 65–100More Less▪ Abstract This review summarizes recent information concerning the pharmacological and toxicological significance of the human flavin-containing monooxygenase (FMO, EC 1.14.13.8). The human FMO oxygenates nucleophilic heteroatom-containing chemicals and drugs and generally converts them into harmless, polar, readily excreted metabolites. Sometimes, however, FMO bioactivates chemicals into react Read More
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CANNABINOID RECEPTORS AS THERAPEUTIC TARGETS
Vol. 46 (2006), pp. 101–122More Less▪ Abstract CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein–coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by agonists or antagonists, or indirectly by manipulating endocannabinoid metabolism. I Read More
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REGULATION OF DRUG-METABOLIZING ENZYMES AND TRANSPORTERS IN INFLAMMATION
Vol. 46 (2006), pp. 123–149More Less▪ Abstract Inflammation and infection have long been known to downregulate the activity and expression of cytochrome P450 (CYP) enzymes involved in hepatic drug clearance. This can result in elevated plasma drug levels and increased adverse effects. Recent information on regulation of human CYP enzymes is presented, as are new developments in our understanding of the mechanisms of regulation. Experiments to s Read More
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ACCESSORY PROTEINS FOR G PROTEINS: Partners in Signaling
Vol. 46 (2006), pp. 151–187More Less▪ Abstract Accessory proteins involved in signal processing through heterotrimeric G proteins are generally defined as proteins distinct from G protein–coupled receptor (GPCR), G protein, or classical effectors that regulate the strength/efficiency/specificity of signal transfer upon receptor activation or position these entities in the right microenvironment, contributing to the formation of a functional signal transduction comp Read More
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THE PROTEASOME AND PROTEASOME INHIBITORS IN CANCER THERAPY
Vol. 46 (2006), pp. 189–213More Less▪ Abstract The proteasome, a multicatalytic proteinase complex, is responsible for the majority of intracellular protein degradation. Pharmacologic inhibitors of the proteasome possess in vitro and in vivo antitumor activity, and bortezomib, the first such agent to undergo clinical testing, has significant efficacy against multiple myeloma and non-Hodgkin lymphoma (NHL). Preclinical studies demonstrate that protea Read More
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NUCLEAR AND MITOCHONDRIAL COMPARTMENTATION OF OXIDATIVE STRESS AND REDOX SIGNALING
Vol. 46 (2006), pp. 215–234More Less▪ Abstract New methods to measure thiol oxidation show that redox compartmentation functions as a mechanism for specificity in redox signaling and oxidative stress. Redox Western analysis and redox-sensitive green fluorescent proteins provide means to quantify thiol/disulfide redox changes in specific subcellular compartments. Analyses using these techniques show that the relative redox states from most reducing to most o Read More
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THE REGULATION AND PHARMACOLOGY OF ENDOTHELIAL NITRIC OXIDE SYNTHASE
Vol. 46 (2006), pp. 235–276More Less▪ Abstract Nitric oxide (NO) is a small, diffusible, lipophilic free radical gas that mediates significant and diverse signaling functions in nearly every organ system in the body. The endothelial isoform of nitric oxide synthase (eNOS) is a key source of NO found in the cardiovascular system. This review summarizes the pharmacology of NO and the cellular regulation of endothelial NOS (eNOS). The molecular intricacies of the che Read More
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REGULATION OF PLATELET FUNCTIONS BY P2 RECEPTORS
Vol. 46 (2006), pp. 277–300More Less▪ Abstract The main role of blood platelets is to ensure primary hemostasis, which is the maintenance of vessel integrity and cessation of bleeding upon injury. While playing a major part in acute arterial thrombosis, platelets are also involved in inflammation, atherosclerosis, and angiogenesis. ADP and ATP play a crucial role in platelet activation, and their receptors are potential targets for antithrombotic drugs. The ATP-gated c Read More
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FUNCTIONAL IMAGING OF TUMOR PROTEOLYSIS
Vol. 46 (2006), pp. 301–315More Less▪ Abstract The roles of proteases in cancer are now known to be much broader than simply degradation of extracellular matrix during tumor invasion and metastasis. Furthermore, proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, endothelial cells) as well as tumor cells are recognized to contribute to pathways critical to neoplastic progression. Although elevated expression (transcripts and pr Read More
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PHARMACOGENOMICS OF ACUTE LEUKEMIA
Vol. 46 (2006), pp. 317–353More Less▪ Abstract Over the past four decades, treatment of acute leukemia in children has made remarkable progress, from this disease being lethal to now achieving cure rates of 80% for acute lymphoblastic leukemia and 45% for acute myeloid leukemia. This progress is largely owed to the optimization of existing treatment modalities rather than the discovery of new agents. However, the annual number of patients with leu Read More
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REGULATION OF PHOSPHOLIPASE C ISOZYMES BY RAS SUPERFAMILY GTPASES
Vol. 46 (2006), pp. 355–379More Less▪ Abstract The physiological effects of many extracellular stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid-signaling pathways. These signaling responses include the classically described conversion of PtdIns(4,5)P2 to the Ca2+-mobilizing second messenger Ins(1,4,5)P3 and the protein kinase C–activating second messenger diacylglycerol as well as a Read More
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ROLE OF ABCG2/BCRP IN BIOLOGY AND MEDICINE
Vol. 46 (2006), pp. 381–410More Less▪ Abstract The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must homodimerize to acquire transport activity. ABCG2 is found in a variety of stem cells and may prot Read More
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CO AS A CELLULAR SIGNALING MOLECULE
Vol. 46 (2006), pp. 411–449More Less▪ Abstract Many biological functions of heme oxygenase (HO), such as cytoprotection against oxidative stress, vasodilation, neurotransmission in the central or peripheral nervous systems, and anti-inflammatory, anti-apoptotic, or anti-proliferative potential, have been attributed to its enzymatic byproduct carbon monoxide (CO), although roles for biliverdin/bilirubin and iron have also been proposed. In addition to these Read More
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FUNCTION OF RETINOID NUCLEAR RECEPTORS: Lessons from Genetic and Pharmacological Dissections of the Retinoic Acid Signaling Pathway During Mouse Embryogenesis
Vol. 46 (2006), pp. 451–480More Less▪ Abstract Retinoic acid (RA) is involved in vertebrate morphogenesis, growth, cellular differentiation, and tissue homeostasis. The use of in vitro systems initially led to the identification of nuclear receptor RXR/RAR heterodimers as possible transducers of the RA signal. To unveil the physiological functions of RARs and RXRs, genetic and pharmacological studies have been performed in the mouse. Together, their resul Read More
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MOLECULAR MECHANISM OF 7TM RECEPTOR ACTIVATION—A GLOBAL TOGGLE SWITCH MODEL
Vol. 46 (2006), pp. 481–519More Less▪ Abstract The multitude of chemically highly different agonists for 7TM receptors apparently do not share a common binding mode or active site but nevertheless act through induction of a common molecular activation mechanism. A global toggle switch model is proposed for this activation mechanism to reconcile the accumulated biophysical data supporting an outward rigid-body movement of the intracellular segments, as Read More
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Previous Volumes
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Volume 64 (2024)
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Volume 63 (2023)
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Volume 62 (2022)
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Volume 61 (2021)
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Volume 60 (2020)
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Volume 59 (2019)
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Volume 58 (2018)
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Volume 57 (2017)
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Volume 56 (2016)
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Volume 55 (2015)
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Volume 54 (2014)
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Volume 53 (2013)
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Volume 52 (2012)
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Volume 51 (2011)
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Volume 50 (2010)
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Volume 49 (2009)
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Volume 48 (2008)
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Volume 47 (2007)
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Volume 46 (2006)
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Volume 45 (2005)
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Volume 44 (2004)
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Volume 43 (2003)
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Volume 42 (2002)
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Volume 41 (2001)
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Volume 40 (2000)
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Volume 39 (1999)
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Volume 38 (1998)
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Volume 37 (1997)
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Volume 36 (1996)
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Volume 35 (1995)
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Volume 34 (1994)
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Volume 33 (1993)
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Volume 32 (1992)
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Volume 31 (1991)
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Volume 30 (1990)
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Volume 29 (1989)
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Volume 28 (1988)
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Volume 27 (1987)
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Volume 26 (1986)
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Volume 25 (1985)
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Volume 24 (1984)
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Volume 23 (1983)
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Volume 22 (1982)
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Volume 21 (1981)
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Volume 20 (1980)
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Volume 19 (1979)
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Volume 18 (1978)
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Volume 17 (1977)
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Volume 16 (1976)
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Volume 15 (1975)
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Volume 14 (1974)
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Volume 13 (1973)
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Volume 12 (1972)
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Volume 11 (1971)
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Volume 10 (1970)
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Volume 9 (1969)
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Volume 8 (1968)
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Volume 7 (1967)
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Volume 6 (1966)
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Volume 5 (1965)
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Volume 4 (1964)
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Volume 3 (1963)
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Volume 2 (1962)
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Volume 1 (1961)
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Volume 0 (1932)