ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00149.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The first issue of Acta pharmacologica et toxicologica was circulated on May 5th, 1945, the very day on which World War II ended in Denmark. The journal is the official publication medium of the Scandinavian Pharmacological Societies. The societies are also represented by associate editors in the editorial board of Pharmacological Reviews. On the happy occasion of the anniversary, we were pleased to receive the following congratulation address from the editor of Pharmacological Reviews, James A. Bain, Ph.D., past president of the International Union of Pharmacology, and Professor of Pharmacology, School of Medicine Emory University, Atlanta, Georgia 30322, U.S.A.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00150.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Little has been known of the abundance in the brain of any of the G protein coupled P2purinoceptors nor their pharmacology. Here we show that [35S]dATPαS is a suitable radioligand for investigating these receptors and hence that they are exceptionally abundant both in one‐day‐old chick (Bmax: 37 pmol agonist sites/mg protein) and adult rat brain membranes (Bmax: 39 pmol/mg protein). [35S]dATPαS (which is selective for P2Yover the P2Xtypes of purinoceptor) binds with high affinity to these sites in the chick (Kd: 13.3 nM) and in the rat brain membranes (Kd; 9.1 nM). The rank order of potency of purinoceptor‐active agonists and antagonists displacing [35S]dATPαS binding is: dATPαS>(3′‐deoxyATP, 2‐methylthioATP ATPαS, ATP)>2′‐deoxyATP>2‐methylthioADP>ADP>>suramin, Reactive Blue‐2>>UTR L‐β, γ‐methyleneATP, adenosine; this defines these binding sites as P2Ysubtypes of the P2purinoceptors. This pharmacological profile of purinergic ligands is in excellent agreement with the potency order established for the recombinant P2Y1purinoceptor from chick brain, identifying the great majority of the brain P2purinoceptors as identical or very simi

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00151.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Many receptors stimulate proliferation of NIH 3T3 cells in a ligand dependent fashion. Based on this observation, we developed a high throughput assay of cloned receptor pharmacology. In this assay, receptors are transiently co‐expressed with the marker enzyme β‐galactosidase. Receptors that induce cellular proliferation select and amplify the cells that also express the marker, thus the ability of ligands to alter receptor activity are reported as changes in enzyme activity. In the present study, we used this assay to evaluate the ability of agonist ligands to stimulate four cloned receptors. The agonists phenylephrine, carbachol, substance P and nerve growth factor selectively stimulated cells transfected with the α‐1b adrenergic, m4 muscarinic, NK1 neurokinin and trkA neurotrophin receptors, respectively. These data demonstrate that a high throughput colorimetric assay performed in 96 well plates can be used to evaluate the pharmacology of ligands for cloned receptors belonging to a wide range of functional and pharmacological

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00152.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00153.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Antipsychotic agents share the ability to antagonize dopamine (DA) receptors, and correlation studies have indicated that the clinical efficacy of neuroleptic agents may be coupled to their affinity for D2receptors. More recently, a family of DA D2‐like receptors has been identified. These receptors include the D2A, D2B, D3and D4receptors. On the basis ofin vitroreceptor‐binding studies, it has been suggested that the atypical profile of clozapine might be related to a selective effect on the D4receptor subtype. We have studied the receptor‐binding profiles of a series of antipsychotic agents and evaluated some of the compounds in behavioural assays in the rat. Most of the antipsychotic agents lack selectivity for DA‐receptors as well as selectivity for the various DA‐receptor subtypes. Because of this lack of selectivity, it is impossible to draw firm conclusions about the role of any particular receptor in the clinical profile of the neuroleptic agents. Furthermore, the pharmacology of potential human metabolites has to be taken into account in a proper analysis of the clinical profile. Consequently, most speculations on the key‐target of clinically interesting antipsychotics (including clozapine) may be of little practical value. Clinical studies with receptor (subtype)‐selective agents will be mor

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00154.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Since the metabolism of most foreign compounds is predominantly controlled by hepatic in metabolism, isolated hepatocytes in most cases quite well predict the pattern of the overall metabolism of a given compound. Methods have been developed for cryopreserving isolated hepatocytes from man and other species with satisfactory maintenance of foreign compound metabolizing enzyme activities. The installation of a bank of cryopreserved hepatocytes from different species is possible and may be used for rational species extrapolation. It is necessary for some toxicological investigations to have hepatocytes which retain their differentiated status in culture for a sufficient time period. This might be achieved by co‐culturing hepatocytes with diverse cell lines. However, from one cell line to the other differences in the pattern of stabilization of individual hepatocyte functions are found. In addition, questions on metabolic action of individual isoenzymes can also be addressed by the use of genetically engineered cell lines. All thein vitrosystems mentioned, especially those which contain differentiated human cells or human isoenzymes are helpful in the rational species extrapolation of toxic effects from animal to ma

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00155.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:A yeast dioxin receptor chimera model has been developed to study ligand binding and transactivation properties of the human dioxin receptor. Using this new yeast model, the human dioxin receptor chimera was found to possess a constitutive transactivity on aLacZreporter gene, however, the transactivation by the chimera was enhanced by the addition of several polycyclic aromatic hydrocarbons to the culture medium. The order of best polycyclic aromatic hydrocarbon inducer to worst correlated well with the knownin vitrodioxin receptor binding affinities for these polycyclic aromatic hydrocarbons. 7, 8‐Benzoflavone, a weak dioxin receptor agonist and strong antagonist of the mammalian dioxin receptor also behaved as a weak agonist and strong antagonist of the human dioxin receptor chimera expressed in yeast. The implications for these findings as well as the utility of this new yeast human dioxin receptor chimera model are discusse

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00156.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00157.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY