abstract：:The vascular Na+ pump maintains intracellular ionic concentration and controls membrane potential. Its inhibition by cardiac glycosides enhances the intracellular Na+ concentration. This in turn activates the Na+-Ca2+ exchange mechanism, which induces intracellular Ca2+ increase, membrane depolarization, and noradrena...

journal_title：Pharmacology & therapeutics

authors： Marín J,Redondo J

更新日期：1999-12-01 00:00:00

abstract：:It is now generally accepted that protein phosphorylation-dephosphorylation has a role in the regulation of essentially all cellular functions. Thus, it is of interest that this process is involved in signal transduction. Nonetheless, the extent to which protein phosphorylation participates in signaling is truly remar...

journal_title：Pharmacology & therapeutics

authors： Graves JD,Krebs EG

更新日期：1999-05-01 00:00:00

abstract：:Protein tyrosine kinases (PTKs) play a key role in normal cell and tissue development. Enhanced PTK activity is intimately correlated with proliferative diseases, such as cancers, leukemias, psoriasis, and restenosis. This realization prompted us to systematically synthesize tyrosine phosphorylation inhibitors (tyrpho...

journal_title：Pharmacology & therapeutics

authors： Levitzki A

更新日期：1999-05-01 00:00:00

abstract：:Protein phosphorylation is the major post-translational modification used by eukaryotic cells to control cellular signaling. Protein kinases have emerged as attractive drug targets because heightened protein kinase activity has been associated with several proliferative diseases, most notably cancer and restenosis. Un...

journal_title：Pharmacology & therapeutics

authors： Bishop AC,Shokat KM

更新日期：1999-05-01 00:00:00

abstract：:The gene MUC1 encodes a large membrane-associated glycoprotein, previously termed polymorphic epithelial mucin and now known as MUC1. The majority of the extracellular domain is made up of tandem repeats of 20 amino acids. In some epithelial malignancies, MUC1 is up-regulated, and as a result of changes in glycosyl an...

journal_title：Pharmacology & therapeutics

authors： Miles DW,Taylor-Papadimitriou J

更新日期：1999-04-01 00:00:00

abstract：:It is surprising that only relatively recently has attention been directed to the characterization of the properties of acid ribonucleases (RNases), leading to some understanding of their biochemistry and their functional roles. The present review summarizes current progress in this field under the following general t...

journal_title：Pharmacology & therapeutics

authors： Irie M

更新日期：1999-02-01 00:00:00

abstract：:During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two famil...

journal_title：Pharmacology & therapeutics

authors： Jose PA,Eisner GM,Felder RA

更新日期：1998-11-01 00:00:00

abstract：:The 90-kDa molecular chaperone family (which comprises, among other proteins, the 90-kDa heat-shock protein, hsp90 and the 94-kDa glucose-regulated protein, grp94, major molecular chaperones of the cytosol and of the endoplasmic reticulum, respectively) has become an increasingly active subject of research in the past...

journal_title：Pharmacology & therapeutics

authors： Csermely P,Schnaider T,Soti C,Prohászka Z,Nardai G

更新日期：1998-08-01 00:00:00

abstract：:S-Adenosylhomocysteine (AdoHcy), formed after the donation of the methyl group of S-adenosylmethionine to a methyl acceptor, is hydrolyzed to adenosine and homocysteine by AdoHcy hydrolase physiologically. The administration of the inhibitors of AdoHcy hydrolase to cells or animals normally results in an accumulation ...

journal_title：Pharmacology & therapeutics

authors： Chiang PK

更新日期：1998-02-01 00:00:00

abstract：:This review focuses on the chemical and enzymatic aspects of the reductive activation of mitomycin C, its disulfide analogs KW-2149 and BMS-181174, and, in less detail, FR66979 and FR900482, newly discovered antitumor antibiotics related to mitomycins. Furthermore, structural aspects of DNA damage induced by these dru...

journal_title：Pharmacology & therapeutics

authors： Tomasz M,Palom Y

更新日期：1997-10-01 00:00:00

abstract：:This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catal...

journal_title：Pharmacology & therapeutics

authors： Horsch M,Mayer C,Sennhauser U,Rast DM

更新日期：1997-10-01 00:00:00

abstract：:Experimental and clinical studies suggest that the central and peripheral benzodiazepine (BDZ) receptors together with their ligands form the molecular basis of a novel regulatory network that contributes to the effects of anxiety on immune status. The peripheral-type receptors located on phagocytes and glial cells ap...

journal_title：Pharmacology & therapeutics

authors： Zavala F

更新日期：1997-09-01 00:00:00

abstract：:The smooth muscle of the normal bladder wall must have some specific properties. It must be very compliant and able to reorganise itself during filling and emptying to accommodate the change in volume without generating any intravesical pressure, but whilst maintaining the normal shape of the bladder. It must be capab...

journal_title：Pharmacology & therapeutics

authors： Turner WH,Brading AF

更新日期：1997-08-01 00:00:00

abstract：:Ion channels play key roles in determining smooth muscle tone by setting the membrane potential and allowing Ca2+ influx. Perhaps not surprisingly, therefore, they also provide targets for neurotransmitters and other messengers that act on smooth muscle. Application of patch-clamp and molecular biology techniques and ...

journal_title：Pharmacology & therapeutics

authors： Beech DJ

更新日期：1997-01-01 00:00:00

abstract：:There are at least two types of cannabinoid receptors, CB1 and CB2, both coupled to G-proteins. CB1 receptors are present in the central nervous system and CB1 and CB2 receptors in certain peripheral tissues. The existence of endogenous cannabinoid receptor agonists has also been demonstrated. These discoveries have l...

journal_title：Pharmacology & therapeutics

authors： Pertwee RG

更新日期：1997-01-01 00:00:00

abstract：:Angiotensin II (Ang II) is the main effector hormone of the renin-angiotensin system (RAS). The pathogenesis of many cardiovascular diseases, including heart failure and hypertension, appear to be related to Ang II production. The generation of Ang II involves angiotensin-converting enzyme (ACE) in circulating and tis...

journal_title：Pharmacology & therapeutics

authors： Davis GK,Roberts DH

更新日期：1997-01-01 00:00:00

abstract：:The aromatic amine 2-acetylaminofluorene (AAF) produced neoplasms in diverse target organs of many animal species. AAF was DNA-reactive after N-hydroxylation by CYP1A2 in the liver and nitrenium ion formation at the target site. In mouse bladder, AAF-DNA adducts were proportional to dose. An epigenetic component for t...

journal_title：Pharmacology & therapeutics

authors： Verna L,Whysner J,Williams GM

更新日期：1996-01-01 00:00:00

abstract：:gamma-Aminobutyric acid (GABA)A receptors for the inhibitory neurotransmitter GABA are likely to be found on most, if not all, neurons in the brain and spinal cord. They appear to be the most complicated of the superfamily of ligand-gated ion channels in terms of the large number of receptor subtypes and also the vari...

journal_title：Pharmacology & therapeutics

authors： Johnston GA

更新日期：1996-01-01 00:00:00

abstract：:The physiological role of K+ channel opening by endogenous substances (e.g., neurotransmitters and hormones) is a recognised inhibitory mechanism. Thus, the identification of novel synthetic molecules that 'directly' open K+ channels has led to a new direction in the pharmacology of ion channels. The existence of many...

journal_title：Pharmacology & therapeutics

authors： Lawson K

更新日期：1996-01-01 00:00:00

abstract：:Unwanted cells are removed by physiological cell death processes that are highly conserved throughout the animal kingdom. Physiological cell death plays an important role in development, tissue homeostasis and defence against viral infection and mutation. This review describes the molecular components that implement t...

journal_title：Pharmacology & therapeutics

authors： Uren AG,Vaux DL

更新日期：1996-01-01 00:00:00

abstract：:Therapeutic strategies based on the insertion of cytokine genes into the genome of tumour cells, followed by vaccination with the resulting genetically modified, cytokine-producing cells, represent a new potential prospect for treatment of cancer patients. In this review, the concept of cytokine gene-modified cancer v...

journal_title：Pharmacology & therapeutics

authors： Bubenik J

更新日期：1996-01-01 00:00:00

abstract：:Hybrid polar compounds, of which hexamethylene bisacetamide (HMBA) is the prototype, have been shown to be potent inducers of differentiation of many types of transformed cells. With virus-transformed murine erythroleukemia cells as a model, HMBA was shown to cause these cells to arrest in G1 phase and express globin ...

journal_title：Pharmacology & therapeutics

authors： Rifkind RA,Richon VM,Marks PA

更新日期：1996-01-01 00:00:00

abstract：:The pharmaceutical industry offers the world's population alleviation and cure from a variety of medical conditions, while also contributing to the economic performance of many countries. The potential importance of these characteristics have made the industry an area of intense debate, criticism and praise. This revi...

journal_title：Pharmacology & therapeutics

authors： Craig AM,Malek M

更新日期：1995-05-01 00:00:00

abstract：:In the search for new approaches to cancer therapy, the first alkyllysophospholipid (ALP) analogs were designed and studied about two decades ago, either as potential immunomodulators or as antimetabolites of phospholipid metabolism. In the meantime, it has been demonstrated that they really act in this way. However, ...

journal_title：Pharmacology & therapeutics

authors： Brachwitz H,Vollgraf C

更新日期：1995-04-01 00:00:00

abstract：:Severe and prolonged impairment of mitochondrial beta-oxidation leads to microvesicular steatosis, and, in severe forms, to liver failure, coma and death. Impairment of mitochondrial beta-oxidation may be either genetic or acquired, and different causes may add their effects to inhibit beta-oxidation severely and trig...

journal_title：Pharmacology & therapeutics

authors： Fromenty B,Pessayre D

更新日期：1995-01-01 00:00:00

abstract：:Astroglial cells express neurotrophic and/or neurite growth-promoting factors, including (a) peptide growth factors (e.g. nerve growth factors, ciliary neuronotrophic factor, fibroblast growth factor), (b) neurotransmitters (such as glutamate, neuropeptide Y), (c) cell adhesion molecules (e.g. N-CAM) and (d) extracell...

journal_title：Pharmacology & therapeutics

authors： Müller HW,Junghans U,Kappler J

更新日期：1995-01-01 00:00:00

abstract：:The demonstration that RNA can be cleaved by cis or trans ribozymes (catalytic RNAs, RNA enzymes) has potentially important therapeutic implications. Since their discovery in the 1980s, the biochemistry and conserved sequences of ribozymes have been well characterized. Ribozymes are effective modulators of gene expres...

journal_title：Pharmacology & therapeutics

authors： Kijima H,Ishida H,Ohkawa T,Kashani-Sabet M,Scanlon KJ

更新日期：1995-01-01 00:00:00

abstract：:This article reviews uses of metabolic suicide genes in gene therapy. Suicide genes encode novel nonmammalian enzymes that can convert a relatively nontoxic prodrug into a highly toxic agent. Cells genetically transduced to express such genes essentially commit metabolic suicide in the presence of the appropriate prod...

journal_title：Pharmacology & therapeutics

authors： Mullen CA

更新日期：1994-08-01 00:00:00

abstract：:We review the adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the small and large intestine. NSAIDs cause small intestinal inflammation in 65% of patients receiving the drugs long-term. The clinical implications of NSAID-induced enteropathy are that patients bleed and lose protein from the inflamma...

journal_title：Pharmacology & therapeutics

authors： Bjarnason I,Macpherson AJ

更新日期：1994-04-01 00:00:00

abstract：:Venoms from stonefish (genus Synanceja) have marked effects on the cardiovascular and neuromuscular systems and on vascular permeability; the venoms also exhibit haemolytic and hyaluronidase activity. Recently, a toxic protein, stonustoxin (SNTX), was purified from the venom of S. horrida: the primary lethal action of...

journal_title：Pharmacology & therapeutics

authors： Gwee MC,Gopalakrishnakone P,Yuen R,Khoo HE,Low KS

更新日期：1994-01-01 00:00:00

abstract：:In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis st...

journal_title：Pharmacology & therapeutics

authors： Chopin P,Moret C,Briley M

更新日期：1994-01-01 00:00:00

abstract：:The integration of retroviral DNA appears to be obligatory for the efficient replication of retroviruses in their respective host cells. During a natural infection, integration takes place in a process that includes biochemically and temporally discrete steps. These are: (1) the removal of two nucleotides from the 3' ...

journal_title：Pharmacology & therapeutics

authors： Kulkosky J,Skalka AM

更新日期：1994-01-01 00:00:00

abstract：:Adipocyte hyperplasia occurs by the proliferation and differentiation of adipocyte precursor cells or preadipocytes. Although the process of commitment to the adipocyte lineage is poorly understood, a great deal of information has accumulated about the processes and regulatory mechanisms involved in preadipocyte diffe...

journal_title：Pharmacology & therapeutics

authors： Butterwith SC

更新日期：1994-01-01 00:00:00

abstract：:Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors are a class of lipid-lowering medications, with a major activity on plasma cholesterol levels, now enjoying a vast popularity among physicians and patients. These drugs, affecting a very early and key step of sterol biosynthesis, differ to a large extent ...

journal_title：Pharmacology & therapeutics

authors： Sirtori CR

更新日期：1993-12-01 00:00:00

abstract：:Three separate experimental approaches, using site-selective cAMP analogs, antisense strategy and retroviral vector-mediated gene transfer, have provided evidence that two isoforms, the RI- and RII-regulatory subunits of cAMP-dependent protein kinase, have opposite roles in cell growth and differentiation; RI being gr...

journal_title：Pharmacology & therapeutics

authors： Cho-Chung YS,Clair T

更新日期：1993-11-01 00:00:00

abstract：:Despite difficulties in the interpretation of available data, certain general observations can be made on the epidemiology of poisioning. Childhood poisoning is usually accidental and tends to be associated with a low morbidity and mortality. In Western Europe and North America, it is most often due to household produ...

journal_title：Pharmacology & therapeutics

authors： Meredith TJ

更新日期：1993-09-01 00:00:00

abstract：:Polymorphisms have been detected in a variety of xenobiotic-metabolizing enzymes at both the phenotypic and genotypic level. In the case of four enzymes, the cytochrome P450 CYP2D6, glutathione S-transferase mu, N-acetyltransferase 2 and serum cholinesterase, the majority of mutations which give rise to a defective ph...

journal_title：Pharmacology & therapeutics

authors： Daly AK,Cholerton S,Gregory W,Idle JR

更新日期：1993-02-01 00:00:00

abstract：:Drug therapy directed toward the fetus would be intended for either treating a fetal disorder or improving the capacity for later intrauterine or postnatal adaptation. Most reported trials involve single cases or small numbers of fetuses receiving the drug transplacentally after the first trimester, but before attaini...

journal_title：Pharmacology & therapeutics

authors： Rayburn WF,Payne GG Jr

更新日期：1993-01-01 00:00:00

abstract：:The endothelins and sarafotoxins are two structurally related families of potent vasoactive peptides. Although the physiological functions of these peptides are not entirely clear, the endothelins are probably involved in pathophysiological conditions such as hypertension and heart failure. This review summarizes the ...

journal_title：Pharmacology & therapeutics

authors： Sokolovsky M

更新日期：1992-01-01 00:00:00

abstract：:Polycyclic aromatic hydrocarbons (PAH) are carcinogens requiring metabolic activation to react with cellular macromolecules, the initial event in carcinogenesis. Cytochrome P450 mediates binding of PAH to DNA by two pathways of activation. One-electron oxidation to form radical cations is the major pathway of activati...

journal_title：Pharmacology & therapeutics

authors： Cavalieri EL,Rogan EG

更新日期：1992-01-01 00:00:00