1,720,958 research outputs found
In vitro and in vivo modulation of cholinergic muscarinic receptors in rat lymphocytes and brain by cholinergic agents
No full textA binding site for 3H-quinuclidinyl benzylate (QNB) has been identified in rat lymphocytes which has the characteristics of a cholinergic muscarinic receptor (Costa, L. G., Kaylor, G. & Murphy, S. D. (1988). Muscarinic cholinergic binding sites on rat lymphocytes. Immunopharmacology, 16, 139-149.) Here we show that prolonged exposures to cholinergic compounds in vitro and in vivo modulate muscarinic receptor binding in lymphocytes as well as in brain tissue. Exposure of rat splenic lymphocytes in vitro to oxotremorine caused a time- and concentration-dependent decrease in the density of 3H-QNB binding sites. This decrease occurred only when incubation with oxotremorine was carried out at 37 degrees C and not at 0-4 degrees C, suggesting that it was not an artifact due to residual, unwashed, oxotremorine. The effect of oxotremorine was mimicked by two other cholinergic agonists, acetylcholine and carbachol, and was antagonized by atropine, which, when present alone, caused an increase in 3H-QNB binding. In vivo exposures to oxotremorine or atropine (both at 20 mg/kg/day for 14 days via an ALZA minipump) caused a significant decrease (20-30%) and increase (13-30%), respectively, of 3H-QNB binding in various brain areas as well as circulating lymphocytes. Repeated administrations of the organophosphorus insecticide disulfoton (2 mg/kg/day for 14 days, i.p.) caused significant reductions (59-88%) of acetylcholinesterase activity in brain, lymphocytes, plasma and red blood cells, as well as a 23-39% decrease of 3H-QNB binding in brain areas and circulating lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS
Interaction of choline with muscarine receptor-stimulated phosphoinositide metabolism in the rat brain
No full textPrevious receptor binding studies had shown that choline can interact with low potency with muscarine cholinoceptors. In the present study we have investigated whether choline is capable of functionally activating muscarine receptors by investigating its ability in stimulating the hydrolysis of phosphoinositides, a response believed to be coupled in brain to the M1 subtype of muscarine receptors. The results indicated that choline was only a very weak inducer of inositol phosphates (InsPs) accumulation in rat cerebral cortex slices as compared with acetylcholine or charbachol. Maximal increase of InsPs accumulation, at a choline concentration of 10 mM, was only 39 +/- 7%, as compared with the 4- to 6-fold stimulation induced by the other compounds. This effect of choline was not modified by physostigmine nor by the uptake inhibitor hemicholinium-3. At high concentrations, however, choline antagonized the stimulatory effect of acetylcholine and carbachol, suggesting that it might act as a partial agonist at this subtype of muscarine receptors, similar to what has been observed with oxotremorine. Choline had no effect on noradrenaline-stimulated InsPs accumulation
Muscarinic cholinergic binding sites on rat lymphocytes
No full textReceptors for neurotransmitters in blood cells could serve as useful markers for the same receptors in solid tissues. Muscarinic receptors have been identified in human, rat and mouse lymphocytes by binding of [3H]quinuclidinyl benzilate (3H-QNB); however, the biochemical and pharmacological characterization of such binding sites has not been complete. Spleen lymphocytes were isolated on a histopaque gradient and incubated in Hank's buffer with 3H-QNB. Binding of 3H-QNB was linear with increasing protein concentrations and was saturable. Binding constants were Bmax = 111 +/- 10.5 fmol/10(6) cells, and Kd = 29.7 +/- 3.9 nM (n = 7). An extensive pharmacological analysis of these binding sites indicated that several cholinergic muscarinic drugs were capable of inhibiting 3H-QNB binding. Muscarinic antagonists were more potent than agonists, and lipophilic drugs were more potent than hydrophilic drugs. Several non-cholinergic drugs were also capable of inhibiting 3H-QNB binding; however, they did so also in brain membranes, while a third group of non-cholinergic drugs and neurotransmitters were inactive. Similar results were also obtained in circulating lymphocytes and in lymphocyte membranes. These results suggest that lymphocytes possess muscarinic receptors which share several, although not all, characteristics of the same receptors in brain and other tissues. Measurement of these binding sites could be useful to monitor the status of muscarinic receptors in solid tissues
Carbachol- and norepinephrine-stimulated phosphoinositide metabolism in rat brain: effect of chronic cholinesterase inhibition
No full textActivation of cholinergic muscarinic receptors leads to several biochemical events including an increased turnover of phosphoinositides. In this study we have investigated whether repeated administration of the organophosphorus insecticide disulfoton, known to cause the development of tolerance to this compound, would affect phosphoinositide metabolism in rat brain. Basal and carbachol-stimulated phosphoinositide metabolism were measured in cerebral cortex slices, by measuring the accumulation of inositol phosphates (InsPs) in the presence of lithium. In control animals carbachol caused a 600% increase in InsPs accumulation with an EC50 of 100 microM. Maximal effect occurred with a LiCl concentration of 7.5 mM and required the presence of calcium. Administration of disulfoton for 10 days (2 mg/kg/day by gavage), decreased the number of muscarinic receptors in cortex from 1.1 to 0.7 pmol/mg of protein without changing the affinity of the receptors (both measured by binding of [3H]quinuclidinyl benzilate). Acetylcholinesterase was inhibited by 85%. Basal InsPs accumulation was unchanged in disulfoton-treated rats, whereas carbachol-stimulated InsPs accumulation decreased by 18%. No changes of norepinephrine-stimulated InsPs formation and of alpha-1 adrenoceptors were present in cortices from disulfoton-treated rats. Recovery of muscarinic receptor binding and carbachol-stimulated InsPs accumulation occurred at a similar rate and was completed 2 to 3 weeks after the end of the treatment, whereas acetylcholinesterase activity was still 38% inhibited 3 weeks later. These results support the hypothesis that a functional adaptation of muscarinic receptors is involved in the development of tolerance to organophosphates
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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