Abstract：
:Lignocaine suppresses insulin-stimulated glucose transport into the cells and insulin-stimulated glycogenesis at doses equivalent to that used in the treatment of muscle pain disorder. We evaluated the direct effect of lignocaine on insulin receptor (IR) kinase activity. After lignocaine (40 mM, approximately equivalent to 1%) or an equal volume (100 microl) saline had been injected into the tibialis anterior muscle of rat, insulin (50 mM g-1 body weight) was administered into the portal vein in vivo. Immunoprecipitation and immunoblotting were used to detect insulin-mediated tyrosine phosphorylation of both IR-beta and insulin receptor substrate (IRS)-1, and insulin-stimulated binding of IRS-1 to p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) in the extracted muscle. In the in vitro study, purified IR from rat liver and/or recombinant IRS-1 protein with adenosine triphosphate were incubated with lignocaine (4 or 40 mM). Lignocaine reduced insulin-stimulated tyrosine phosphorylation of IR-beta to 12.6+/-5.7% (P<0.001), and IRS-1 to 32.1+/-18.8% (P<0.01), and also reduced insulin-stimulated binding of IRS-1 to p85 to 27.4+/-12.7% (P<0.001) relative to control (100%) in muscle in vivo. The in vitro study revealed that lignocaine directly inhibited both basal and insulin-stimulated tyrosine phosphorylation of IR. These results indicate that clinically used doses of lignocaine inhibit insulin signalling in skeletal muscle. The inhibitory effect of lignocaine on tyrosine kinase activity of the IR underlies the suppression of insulin signalling with lignocaine.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Hirose M,Martyn JA,Kuroda Y,Marunaka Y,Tanaka Ydoi
10.1038/sj.bjp.0704691subject
Has Abstractpub_date
2002-05-01 00:00:00pages
76-80issue
1eissn
0007-1188issn
1476-5381journal_volume
136pub_type
杂志文章abstract：:1. We studied the ability of nitric oxide (NO) to physiologically antagonize endothelin-1 (ET-1) induced constrictions in human internal mammary artery (IMA). We also investigated the hypothesis that NO interacts directly with ET-receptor binding in human heart and aorta. 2. ET-1 potently contracted IMA (EC(50) 6.86 n...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703834
更新日期：2001-01-01 00:00:00
abstract：:This paper is intended to assist pharmacologists to make the most of statistical analysis and avoid common errors. A scenario, in which an experimenter performed an experiment in two separate stages, combined the control groups for analysis and found some surprising results, is presented. The consequences of combined ...
journal_title：British journal of pharmacology
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14529.x
更新日期：1992-11-01 00:00:00
abstract：:We have shown earlier that activation of metabotropic glutamate (mGlu) receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus. In an attempt to determine the signal transduction mechanisms involved in ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703905
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1972.tb07255.x
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abstract：:1. 5-Hydroxytryptamine (5-HT) is known to produce a number of different effects in the gastrointestinal tract of various species, and has been proposed to play a key role in a number of intestinal disorders in man, including irritable bowel syndrome (IBS), although the receptors involved have yet to be established. Th...
journal_title：British journal of pharmacology
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doi：10.1038/sj.bjp.0704571
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2009.00244.x
更新日期：2009-10-01 00:00:00
abstract：:1. We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation. 2. Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 tim...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701564
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.13357
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701935
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journal_title：British journal of pharmacology
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doi：10.1111/bph.15300
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
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更新日期：2011-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1988.tb11405.x
更新日期：1988-01-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb07742.x
更新日期：1977-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07569.x
更新日期：1975-07-01 00:00:00
abstract：:1 The effects of isoprenaline, propranolol and phosphodiesterase inhibitors on (3)H-transmitter overflow elicited by low frequency nerve stimulation were determined in the isolated perfused spleen of the cat.2 (-)-Isoprenaline (0.14, 1.4, and 14 nM) produced a concentration-dependent increase in [(3)H]-transmitter ove...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07779.x
更新日期：1978-05-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13320.x
更新日期：1995-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.15036
更新日期：2021-01-01 00:00:00
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doi：10.1038/sj.bjp.0704863
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journal_title：British journal of pharmacology
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doi：10.1111/j.1476-5381.1990.tb12085.x
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更新日期：2000-08-01 00:00:00
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journal_title：British journal of pharmacology
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更新日期：2010-11-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
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更新日期：2012-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb12936.x
更新日期：1985-02-01 00:00:00
abstract：:1. The effects of the muscarinic agonist carbachol on phosphoinositide metabolism and its relationship to alteration of intracellular calcium were examined in SK-N-SH human neuroblastoma cells. Muscarinic receptors on these cells are coupled to phospholipase C and the myo [2-3H]-inositol phosphates resulting from rece...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb12681.x
更新日期：1989-12-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14754
更新日期：2019-09-01 00:00:00
abstract：:1. The kinetics of glycine-sensitive, N-methyl-D-aspartate (NMDA) receptor desensitization were investigated in cultured neurones with the patch clamp technique. 2. The degree of fast NMDA-receptor desensitization was inversely related to glycine concentration. Thus, increasing concentrations of glycine from 30 nM to ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13556.x
更新日期：1993-05-01 00:00:00
abstract：:1. Antilaminin IgG decreased the dF/dt of mouse isolated atria and inhibited the mechanical effect of acetylcholine in a non-competitive fashion. 2. Inhibitors of nicotinic and muscarinic cholinoceptors impaired the negative inotropic action of antilaminin IgG in mouse isolated atria. Hemicholinium and tetrodotoxin al...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11964.x
更新日期：1989-06-01 00:00:00
abstract：:1. The alpha 1-adrenoceptor subtypes mediating contractions of the smooth muscle in human prostatic urethra and branches of internal iliac artery were characterized in isometric contraction experiments. 2. Phenylephrine produced concentration-dependent contractions in both the urethra and artery. These responses were ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb17053.x
更新日期：1994-11-01 00:00:00
abstract：:1. To determine how pretreatment with sulphonylureas alters the beta cell function, mouse islets were cultured (18 - 20 h) without (controls) or with (test) 0.01 microM glibenclamide. Acute responses to glucose were then determined in the absence of glibenclamide. 2. Test islets were insensitive to drugs (sulphonylure...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702731
更新日期：1999-08-01 00:00:00
