Evidence for a central noradrenaline receptor stimulation by clonidine.
TL;DR: Clonidine increased the flexor reflex of spinal rats also after depletion of all known noradrenaline stores, indicating a stimulation of also central noradRenaline receptors.
About: This article is published in Life Sciences.The article was published on 1970-05-01. It has received 545 citations till now. The article focuses on the topics: Stimulation & Dopamine receptor.
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1,451 citations
TL;DR: It is concluded that systemically administered clonidine inhibits the firing of brain NE neurons by acting directly upon adrenergic receptors located on or near the soma of these neurons but that the concomitant inhibition of 5-HT neurons is an indirect effect (possibly secondary to an impairment in noracrenergic transmission).
900 citations
789 citations
TL;DR: The ChEA database allowed us to reconstruct an initial network of transcription factors connected based on shared overlapping targets and binding site proximity, and it is shown how by combining the Connectivity Map with ChEA, it can rank pairs of compounds to be used to target specific transcription factor activity in cancer cells.
Abstract: Motivation: Experiments such as ChIP-chip, ChIP-seq, ChIP-PET and DamID (the four methods referred herein as ChIP-X) are used to profile the binding of transcription factors to DNA at a genome-wide scale. Such experiments provide hundreds to thousands of potential binding sites for a given transcription factor in proximity to gene coding regions.
Results: In order to integrate data from such studies and utilize it for further biological discovery, we collected interactions from such experiments to construct a mammalian ChIP-X database. The database contains 189 933 interactions, manually extracted from 87 publications, describing the binding of 92 transcription factors to 31 932 target genes. We used the database to analyze mRNA expression data where we perform gene-list enrichment analysis using the ChIP-X database as the prior biological knowledge gene-list library. The system is delivered as a web-based interactive application called ChIP Enrichment Analysis (ChEA). With ChEA, users can input lists of mammalian gene symbols for which the program computes over-representation of transcription factor targets from the ChIP-X database. The ChEA database allowed us to reconstruct an initial network of transcription factors connected based on shared overlapping targets and binding site proximity. To demonstrate the utility of ChEA we present three case studies. We show how by combining the Connectivity Map (CMAP) with ChEA, we can rank pairs of compounds to be used to target specific transcription factor activity in cancer cells.
Availability: The ChEA software and ChIP-X database is freely available online at: http://amp.pharm.mssm.edu/lib/chea.jsp
Contact: avi.maayan/at/mssm.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
778 citations
TL;DR: These functional, anatomical and neurochemical correlates of the alpha 2 binding site distribution establish a neurological basis for the complex pharmacological effects of centrally acting alpha 2 agonists.
711 citations
References
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TL;DR: In this article, the reaction between formaldehyde and phenylalanine and phenylethylamine derivatives has been studied under mild conditions and it has been shown that the amines primarily condense with formaldehyde to 1,2,3,4-tetrahydroisoquinolines which are involved in a secondary reaction to become highly fluorescent and at the same time insoluble.
Abstract: The reaction under mild conditions between formaldehyde and phenylalanine and phenylethylamine derivatives has been studied. When the amines included in a dried protein film were exposed to formaldehyde vapour a very intense green to yellow fluorescence was give only by those that as well as being primary amines also have hydroxyl groups at the 3 and 4 positions (3,4-dihydroxyphenylalanine, dopamine, noradrenaline). The 3-OH group seems to be esssential for the reaction. The catechol amines, which are secondary amines (adrenaline, epinine), gave a much weaker fluorescence that developed more slowly.The results obtained on further examination of the reaction favour the view that the amines primarily condense with formaldehyde to 1,2,3,4-tetrahydroisoquinolines which are involved in a secondary reaction to become highly fluorescent and at the same time insoluble. This secondary reaction may be a binding to protein, and oxidation with the formation of double bonds in the heterocyclic ring, or both.
2,583 citations
TL;DR: A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described, utilizing the difference in the activation spectra of the fluoro-phores to identify the two amines.
Abstract: Summary.
A method for chemical assay of small amounts of adrenaline and noradrenaline in tissues is described. The catechol amines are extracted with perchloric acid. The extracts are passed through a cation exchange column (Dowex 50) which takes up the catechol amines. Elution of the amines from the column is performed by hydrochloric acid. Estimation of the two amines in the eluates is made fluorimetrically after oxidation and rearrangement in alkali. Differentiation between adrenaline and noradrenaline is performed by utilizing the difference in the activation spectra of the fluoro-phores.
993 citations
TL;DR: Supporting evidence for apomorphine acts on the dopamine receptors whereas amphetamine acts by releasing dopamine is given by further functional, biochemical and histochemical studies.
Abstract: Sm,-Recently, Ernst (1967) has reported that the apomorphine-induced compulsive gnawing in rats is not mediated via the release of catecholamines, since it is not reduced by the catecholamine synthesis inhibitors a-methyl-3,4dihydroxyphenylalanine and a-methyltyrosine. On the other hand, the gnawing seen after treatment with (+)-amphetamine is blocked by these synthesis inhibitors. Since the apomorphine-induced gnawing requires an intact corpus striatum and gnawing can also be produced by the catecholamine precursor dihydroxyphenylalanine, Ernst (1967) suggested that apomorphine acts on the dopamine receptors whereas amphetamine acts by releasing dopamine. In the present paper supporting evidence for this view is given by further functional, biochemical and histochemical studies. The functional influence of apomorphine on dopamine neurotransmission in the corpus striatum was examined after unilateral removal of the corpus striatum of adult hooded rats weighing about 200 g (And& Dahlstrom & others, 1966a). A possible action of apomorphine on the noradrenaline receptors of the spinal cord was tested in acutely spinalized adult hooded rats by evaluating the changes in the flexor reflex evoked by pinching the hind limbs. The effect of apomorphine on the dopamine and noradrenaline levels of the brain and spinal cord was determined biochemically (Bertler, Carlsson & Rosengren, 1958; Carlsson & Waldeck, 1958) and histochemically (Falck, Hillarp & others, 1962; Dahlstrom & Fuxe, 1964; Hamberger, Malmfors & Sachs, 1965). Function. These studies were made mainly on rats which had been pretreated with reserpine (10 mg/kg i.p., 3 hr) plus a-methyltyrosine methylester (H 44/68, 500mg/kg, i.p., 2 hr) after removal of the left corpus striatum by suction. After this treatment all the operated animals turned towards the unoperated side (cf. And6n & others, 1966a). After injection of apomorphine (1-25 mg/kg s.c.) these rats changed their position and turned or rotated towards the operated side. This effect began about 5 min after the injection and was evident for about 45-60 min. If apomorphine was given to operated rats not pretreated with reserpineH 44/68 combination, this action of apomorphine, like the gnawing, seemed to be less pronounced. If haloperidol (5 mg/kg i.p.) was given 15-20 min after apomorphine all the rats turned from the operated towards the unoperated side in about 15 min and the gnawing ceased. (+)-Amphetamine (0.5-25 mg/kg s.c.), like apomorphine, made the rats turn or rotate towards the operated side. In contrast to apomorphine, however, this action of amphetamine was not seen after pretreatment with reserpine plus H 44/68 (cf. Weissman, Koe & Tenen, 1966; Hanson, 1967; Ernst, 1967). Apomorphine (25 mg/kg s.c.), in contrast to (+)-amphetamine (05-25 mg/kg s.c.) and ~-3,4-dihydroxyphenylalanine (50-75 mg/kg i.v. 2 hr after nialamide 50 mg/kg i.p.), did not cause a definite increase of the flexor reflex in spinalized rats. Chemistry. The biochemical results obtained in unoperated adult hooded rats are presented in Table 1. Apomorphine caused a retardation of the depletion in brain dopamine produced by H 44/68. The difference between the dopamine levels in the apomorphine-H 44/68 group and in the H 44/68 group is statistically significant (P < 0.001, Student’s r-test). This action of apomorphine on the brain dopamine was blocked by haloperidol. The disappearance of noradrenaline from the brain and the spinal cord after H 44/68 did not seem to be influenced by apomorphine. (+)-Amphetamine did not cause any significant retardation of the dopamine and noradrenaline loss after H 44/68.
894 citations
TL;DR: The histochemical fluorescence method of Falck and Hillarp as discussed by the authors for the demonstration of biogenic monoamines is based on the finding that the amines can be condensed with formaldehyde to yield strongly fluorescent compounds, provided that they are enclosed in a dried protein layer, as in freezedried or air-dried tissues.
Abstract: The histochemical fluorescence method of Falck and Hillarp for the demonstration of biogenic monoamines is based on the finding that the amines can be condensed with formaldehyde to yield strongly fluorescent compounds, provided that they are enclosed in a dried protein layer, as in freeze-dried or air-dried tissues. This review deals mainly with certain principal features of the method: its chemistry, sensitivity, specificity and possibilities for histochemical differentiation between the various amines. Some comments are made on certain of the results obtained with this method.
805 citations
TL;DR: A fluorimetric method for the determination of dopamine using differences in fluorescence characteristics at pH about 5.3, microquantities of dopainine can be determined in the presence of at least equal amounts of adrenaline or noradrenaline.
Abstract: Summary.
A fluorimetric method for the determination of dopamine is described. The principle is similar to that employed in the tri-hydroxyindole method for estimating adrenaline and noradrenaline. Utilizing differences in fluorescence characteristics at pH about 5.3, microquantities of dopainine can be determined in the presence of at least equal amounts of adrenaline or noradrenaline.
618 citations