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Showing papers in "Trends in Pharmacological Sciences in 1991"


Journal ArticleDOI
TL;DR: The recent discovery of a pathogenic mutation in the beta-amyloid precursor protein (APP) gene on chromosome 21 suggests that APP Mismetabolism and beta-amide deposition are the primary events in the disease process.

2,279 citations



Journal ArticleDOI
TL;DR: Evidence that synergistic interactions occur between non-genomic and genomic actions of steroids is reviewed, showing that progesterone appears to be one of the most active of the steroids, and its naturally produced metabolites and some synthetic analogs show activities that are different from the parent steroid.

731 citations



Journal ArticleDOI
TL;DR: Recently, Numa's group has reported the cloning and expression of a dihydropyridine-insensitive Ca2+ channel from brain that most closely resembles the P-type channel described by Llinas and colleagues.

602 citations


Journal ArticleDOI
TL;DR: The tissue distribution of phosphodiesterase isoenzymes is compared and the differential effects of inhibition of particular isoenZymes, with differing subcellular localization, on tissue function are discussed.

550 citations


Journal ArticleDOI
TL;DR: The nonpeptide structures described herein are selective and competitive AII receptor antagonists and add another dimension to the arsenal of drugs manipulating the RAS.

520 citations


Journal ArticleDOI
TL;DR: Gerald Marks and colleagues suggest that carbon monoxide, which is formed endogenously from heme catabolism and which shares some of the chemical and biological properties of nitric oxide, may play a similar role.

423 citations


Journal ArticleDOI
TL;DR: It is proposed that separate receptors may be responsible: one sensitive to 2-MeSATP and the other, a 'nucleotide' receptor, sensitive to UTP, which invariably shows similar potency to ATP in systems where 2-MethylthioATP is inactive.

373 citations


Journal ArticleDOI
TL;DR: A number of distinct sites and mechanisms of action have been proposed to explain these diverse effects of IL-1 in the brain, probably involving multiple receptor subtypes and complex interactions with neurotransmitters and neuropeptides.

335 citations


Journal ArticleDOI
TL;DR: It is explained how oocyte expression studies, in concert with immunological and electrophysiological analysis in vivo, are beginning to reveal the subunit compositions of different neuronal nicotinic receptor subtypes.

Journal ArticleDOI
TL;DR: The most familiar usage of animal models of depression is as antidepressant screening tests, but Paul Willner reviews their usage in a different context--as simulations of depression.


Journal ArticleDOI
TL;DR: John Blundell advocates a systems approach to the study of appetite control, where drug-induced changes in feeding should be interpreted according to a system which involves behaviour, peripheral physiology and brain neural pathways.


Journal ArticleDOI
TL;DR: This review discusses how these gene products have begun to reveal some of the molecular details of stimulus-transcription coupling in the nervous system following seizures, and how these genes have provided novel reagents and concepts for investigating the biochemical and cellular sequelae of seizure in the CNS.


Journal ArticleDOI
TL;DR: This review Jacki Crawley integrates the neurophysiological, behavioral, and release studies which demonstrate both excitatory effects of CCK, and facilitatory modulating effects ofCCK on the inhibitory actions of dopamine, in the mesolimbic pathway.

Journal ArticleDOI
TL;DR: The coupling of NPY receptors to various signal transduction mechanisms is reviewed, including inhibition of adenylyl cyclase and stimulation or inhibition of increases in intracellular Ca2+, but a link between individual NPY receptor subtypes and specific signal transduct pathways has not been established.

Journal ArticleDOI
TL;DR: Stefan Nahorski, Ian Ragan and John Challiss discuss this unusual stimulus-dependent form of enzyme inhibition, emphasizing that the selectivity exhibited by lithium depends upon the degree of inositol lipid hydrolysis and polyphosphoinositide dephosphorylation.

Journal ArticleDOI
TL;DR: The neural mechanisms, described here by Ian Stolerman and Mohammed Shoaib, include a primary action on central nicotinic acetylcholine receptors, associated with selective activation of the mesolimbic dopamine system that also mediates other sources of reinforcement.

Journal ArticleDOI
TL;DR: Drago Sliskovic and Andrew White discuss the importance of ACAT in the lipid transport system and the consequences of its inhibition in a variety of tissues, with emphasis on both lipid-lowering and anti-atherosclerotic effects.

Journal ArticleDOI
TL;DR: Findings indicate that benzodiazepines released in the septum, amygdala and hippocampus do indeed physiologically downregulate memory storage processes; moreover, Benzodiazepine release could be modulated by the anxiety and/or stress associated with each type of learning.

Journal ArticleDOI
TL;DR: Evidence from structure-function studies have resulted in identification of some analogues that function as potent antagonists in all systems examined, and various subtypes of bombesin receptors can now be differentiated by these various classes of antagonist.


Journal ArticleDOI
TL;DR: Sulfoconjugation of drugs and small xenobiotic and endogenous compounds in human tissues is primarily catalysed by cytosolic forms of sulfotransferase, which may also be involved in the bioactivation of both therapeutic drugs and carcinogens.

Journal ArticleDOI
TL;DR: How closely do these receptors match the native receptors that have been identified pharmacologically?



Journal ArticleDOI
TL;DR: The current knowledge about the mechanisms involved in NPY signal transduction and the different mechanisms whereby NPY, released by the peripheral nervous system, may influence vascular tone and cardiac function are reviewed.