Abstract:
:1. In the present study we tested the hypothesis that insulin-like growth factor-1 (IGF-1) modulates resting chloride conductance (G(Cl)) of rat skeletal muscle by activating a phosphatase and that the chloride channel, based on the activity of phosphorylating-dephosphorylating pathways, has different sensitivity to specific ligands, such as the enantiomers of 2-(p-chlorophenoxy) propionic acid (CPP). 2. For this purpose G(Cl) in EDL muscle isolated from adult rat was first lowered by treatment with 5 nM 4-beta-phorbol 12,13 dibutyrate (4-beta-PDB), presumably activating protein kinase C (PKC). The effects of IGF-1 and of the enantiomers of CPP on G(Cl) were then tested. 3. IGF-1 (3.3 nM) had no effect of G(Cl) on EDL muscle fibres in normal physiological solution, whereas it completely counteracted the 30% decrease of G(Cl) induced by 4-beta-PDB. No effects of IGF-1 were observed on G(Cl) lowered by the phosphatase inhibitor okadaic acid (0.25 microM). 4. Ceramide, reported to activate on okadaic acid-sensitive phosphatase, mimicked the effects of IGF-1. In fact, N-acetyl-sphingosine (2.5-5 microM), not very effective in control conditions, increased the G(Cl) lowered by the phorbol ester, but not the G(Cl) lowered by okadaic acid. 5. In the presence of 4-beta-PDB, G(Cl) was differently affected by the enantiomers of CPP. The S(-)-CPP was remarkably less potent in producing the concentration-dependent reduction of G(Cl), whereas the R(+)-CPP caused an increase of G(Cl) at all the concentrations tested. 6. In conclusion, the PKC-induced lowering of G(Cl) is counteracted by IGF-1 through an okadaic acid sensitive phosphatase, and this effect can have therapeutic relevance in situations characterized by excessive channel phosphorylation. In turn the phosphorylation state of the channel can modulate the effects and the therapeutic potential of direct channel ligands.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
De Luca A,Pierno S,Liantonio A,Camerino C,Conte Camerino Ddoi
10.1038/sj.bjp.0702107subject
Has Abstractpub_date
1998-10-01 00:00:00pages
477-82issue
3eissn
0007-1188issn
1476-5381journal_volume
125pub_type
杂志文章abstract:BACKGROUND AND PURPOSE:Human lung fibroblasts (HLF) express high levels of the LPA1 receptor, a GPCR that responds to the endogenous lipid mediator, lysophosphatidic acid (LPA). Several molecular species or analogues of LPA exist and have been detected in biological fluids such as serum and plasma. The most widely expr...
journal_title:British journal of pharmacology
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abstract::1. A method is presented which enables the dissociation constant (KI) of a competitive, pseudo-irreversible or non-competitive antagonist-receptor complex to be estimated without knowledge of agonist concentrations. 2. The technique has been tested using sets of concentration-response data which simulated these variou...
journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1994.tb14047.x
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abstract:BACKGROUND AND PURPOSE:Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple or...
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journal_title:British journal of pharmacology
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doi:10.1111/j.1476-5381.1976.tb07650.x
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abstract::1. Pharmacological studies of alpha7 nicotinic acetylcholine receptors are confounded by the fact that rapid desensitization to high agonist concentration causes alpha7 peak responses to occur well in advance of complete solution exchange. For this reason, peak currents are an invalid measure of response to applied ag...
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abstract::1. The effects of methylflavonolamine hydrochloride (4'-methyl-7-(2-hydroxy-3-isopropylamino-propoxy)-flavone hydrochloride, MFA) were investigated and compared with verapamil and papaverine on rabbit isolated aortic strips, which were contracted by noradrenaline, calcium and potassium. 2. Pre-incubation for 25 min wi...
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journal_title:British journal of pharmacology
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abstract::The above article, published by the British Journal of Pharmacology in October 2015 (https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.13259), has been retracted by agreement between the authors, the journal Editor in Chief and John Wiley & Sons Limited. The retraction has been agreed owing to the discovery...
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pub_type: 杂志文章,撤回出版物
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doi:10.1038/sj.bjp.0702738
更新日期:1999-08-01 00:00:00
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journal_title:British journal of pharmacology
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abstract::1. Pre-eclampsia is a serious pregnancy disorder associated with widespread activation of the maternal vascular endothelium. Recent evidence implicates a role for oxidative stress in the aetiology of this condition. 2. Reactive oxygen species, particularly superoxide anions, invokes endothelial cell activation through...
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doi:10.1038/sj.bjp.0706055
更新日期:2005-03-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07445.x
更新日期:1976-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12521
更新日期:2014-02-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1991.tb12545.x
更新日期:1991-12-01 00:00:00
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb09190.x
更新日期:1982-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Carboxylesterases (CEs) metabolize a wide range of xenobiotic substrates including heroin, cocaine, meperidine and the anticancer agent CPT-11. In this study, we have purified to homogeneity human liver and intestinal CEs and compared their ability with hydrolyse heroin, cocaine and CPT-11. EXPE...
journal_title:British journal of pharmacology
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更新日期:2010-08-01 00:00:00
abstract::1. Muscarinic receptors present in the human astrocytoma cell line 1321 N1 were characterized in radioligand binding studies and in functional studies of carbachol-stimulated phosphatidylinositol (PI) turnover. 2. In radioligand binding studies the muscarinic receptor in intact cells could be labelled using [3H]-N-met...
journal_title:British journal of pharmacology
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更新日期:2002-04-01 00:00:00
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更新日期:2005-03-01 00:00:00
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更新日期:2008-07-01 00:00:00
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journal_title:British journal of pharmacology
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更新日期:2001-05-01 00:00:00
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更新日期:2001-05-01 00:00:00
abstract::Preclinical and clinical data suggest that a modification in GABA(B) receptor expression and function may contribute to the symptoms of major depression and the response to antidepressants. This includes laboratory animal experiments demonstrating that antidepressants modify brain GABA(B) receptor expression and funct...
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更新日期:2011-01-01 00:00:00
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更新日期:2014-03-01 00:00:00