Annual Review of Pharmacology and Toxicology
1545-4304
0362-1642
Mỹ
Cơ quản chủ quản: ANNUAL REVIEWS , Annual Reviews Inc.
Lĩnh vực:
PharmacologyToxicology
Các bài báo tiêu biểu
Intracellular Targets of Matrix Metalloproteinase-2 in Cardiac Disease: Rationale and Therapeutic Approaches
Tập 47 Số Volume 47, 2007 - Trang 211-242 - 2007
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-Dioxin and Related Halogenated Aromatic Hydrocarbons: Examination of the Mechanism of Toxicity
Tập 22 Số 1 - Trang 517-554 - 1982
Lipid vs Protein Theories of Alcohol Action in the Nervous System
Tập 36 Số 1 - Trang 185-201 - 1996
Glutamatergic Mechanisms in Schizophrenia Schizophrenia is a chronic, severely disabling brain disorder with symptomatic onset in early adulthood. Typical antipsychotic medications that block dopamine D2 receptors are most effective in treating the psychosis but have limited effects on the negative symptoms and cognitive impairments. Considerable research has demonstrated that noncompetitive NMDA receptor antagonists, the dissociative anaesthetic like phencyclidine and ketamine, reproduce the cardinal symptomatic features of schizophrenia. Postmortem studies reveal variable alterations in glutamate receptors and their modulators in schizophrenia. Several clinical trials indicate agents that enhance NMDA receptor function via the glycine modulatory site reduce negative and variably improve cognitive function in schizophrenics receiving typical antipsychotics. Thus, hypofunction of a subpopulation of cortico-limbic NMDA receptors may participate in the pathophysiology of schizophrenia.
Tập 42 Số 1 - Trang 165-179 - 2002
Eph Receptors and Ephrins: Therapeutic Opportunities The erythropoietin-producing hepatocellular carcinoma (Eph) receptor tyrosine kinase family plays important roles in developmental processes, adult tissue homeostasis, and various diseases. Interaction with Eph receptor-interacting protein (ephrin) ligands on the surface of neighboring cells triggers Eph receptor kinase–dependent signaling. The ephrins can also transmit signals, leading to bidirectional cell contact–dependent communication. Moreover, Eph receptors and ephrins can function independently of each other through interplay with other signaling systems. Given their involvement in many pathological conditions ranging from neurological disorders to cancer and viral infections, Eph receptors and ephrins are increasingly recognized as attractive therapeutic targets, and various strategies are being explored to modulate their expression and function. Eph receptor/ephrin upregulation in cancer cells, the angiogenic vasculature, and injured or diseased tissues also offer opportunities for Eph/ephrin-based targeted drug delivery and imaging. Thus, despite the challenges presented by the complex biology of the Eph receptor/ephrin system, exciting possibilities exist for therapies exploiting these molecules.
Tập 55 Số 1 - Trang 465-487 - 2015
NEONICOTINOID INSECTICIDE TOXICOLOGY: Mechanisms of Selective Action ▪ Abstract The neonicotinoids, the newest major class of insecticides, have outstanding potency and systemic action for crop protection against piercing-sucking pests, and they are highly effective for flea control on cats and dogs. Their common names are acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam. They generally have low toxicity to mammals (acute and chronic), birds, and fish. Biotransformations involve some activation reactions but largely detoxification mechanisms. In contrast to nicotine, epibatidine, and other ammonium or iminium nicotinoids, which are mostly protonated at physiological pH, the neonicotinoids are not protonated and have an electronegative nitro or cyano pharmacophore. Agonist recognition by the nicotinic receptor involves cation-π interaction for nicotinoids in mammals and possibly a cationic subsite for interaction with the nitro or cyano substituent of neonicotinoids in insects. The low affinity of neonicotinoids for vertebrate relative to insect nicotinic receptors is a major factor in their favorable toxicological profile.
Tập 45 Số 1 - Trang 247-268 - 2005
Carcinogenicity of TCDD: Experimental, Mechanistic, and Epidemiologic Evidence
Tập 34 Số 1 - Trang 343-372 - 1994
Neuropeptide Y-Related Peptides and their Receptors--Are the Receptors Potential Therapeutic Drug Targets?
Tập 33 Số 1 - Trang 309-352 - 1993
STRUCTURE-FUNCTION ASPECTS IN THE NITRIC OXIDE SYNTHASES ▪ Abstract Research on the biological roles of nitric oxide has revealed that it functions as an important signal and effector molecule in a variety of physiologic and pathologic settings. In animals, nitric oxide is synthesized enzymatically from l-arginine through the actions of the nitric oxide synthases (NOSs). The three known NOS isoforms are all dimeric, bi-domain enzymes that contain iron protoporphyrin IX, flavin adenine dinucleotide, flavin mononucleotide, and tetrahydrobiopterin as bound prosthetic groups. This chapter summarizes information regarding the structure-function aspects of the NOSs, which includes composition of the domains, the protein residues and regions involved in prosthetic group binding, catalytic properties of the domains, the relationship between dimeric structure and prosthetic group binding and function, and factors that control assembly of NOS in cells. A general model for NOS structure and assembly is presented.
Tập 37 Số 1 - Trang 339-359 - 1997
CYCLOOXYGENASES 1 AND 2 ▪ Abstract Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth. The two isoforms of COX are almost identical in structure but have important differences in substrate and inhibitor selectivity and in their intracellular locations. Protective PGs, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1. In addition to the induction of COX-2 in inflammatory lesions, it is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly that for pain and fever. PGs made by COX-2 are also important in ovulation and in the birth process. The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective PGs in the stomach and kidney made by COX-1. These highly selective COX-2 inhibitors may not only be anti-inflammatory but may also be active in colon cancer and Alzheimer's disease.
Tập 38 Số 1 - Trang 97-120 - 1998