Abstract:
:1. Hypercholesterolaemia often occurs in patients with type 2 diabetes, who therefore encounter administration of HMG-CoA reductase inhibitors. Alteration of pancreatic beta-cell function leading to an impaired insulin secretory response to glucose plays a crucial role in the pathogenesis of type 2 diabetes. Therefore, it is important to examine the effects of HMG-CoA reductase inhibitors on beta-cell function. 2. Cytosolic Ca2+ concentration ([Ca2+]i) plays a central role in the regulation of beta-cell function. The present study examined the effects of HMG-CoA reductase inhibitors on the glucose-induced [Ca2+]i signalling and insulin secretion in rat islet beta-cells. 3. Simvastatin, a lipophilic HMG-CoA reductase inhibitor, at 0.1-3 microg ml(-1) concentration-dependently inhibited the first phase increase and oscillation of [Ca2+]i induced by 8.3 mM glucose in single beta-cells. The less lipophilic inhibitor, simvastatin-acid, inhibited the first phase [Ca2+]i increase but was two orders of magnitude less potent. The hydrophilic inhibitor, pravastatin (100 microg ml(-1), was without effect on [Ca2+]i. 4. Simvastatin (0.3 microg ml(-1)), more potently than simvastatin-acid (30 microg ml(-1)), inhibited glucose-induced insulin secretion from islets, whereas pravastatin (100 microg ml(-1)) had no effect. 5. Whole-cell patch clamp recordings demonstrated a reversible inhibition of the beta-cell L-type Ca2+ channels by simvastatin, but not by pravastatin. Simvastatin also inhibited the [Ca2+]i increases by L-arginine and KCl, agents that act via opening of L-type Ca2+ channels. 6. In conclusion, lipophilic HMG-CoA reductase inhibitors can inhibit glucose-induced [Ca2+]i signalling and insulin secretion by blocking L-type Ca2+ channels in beta-cells, and their inhibitory potencies parallel their lipophilicities. Precaution should be paid to these findings when HMG-CoA reductase inhibitors are used clinically, particularly in patients with type 2 diabetes.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Yada T,Nakata M,Shiraishi T,Kakei Mdoi
10.1038/sj.bjp.0702397subject
Has Abstractpub_date
1999-03-01 00:00:00pages
1205-13issue
5eissn
0007-1188issn
1476-5381journal_volume
126pub_type
杂志文章abstract::1. The effects of sulphone have been studied on kinin production in dog plasma and on capillary permeability in the skin of rabbits.2. Dog plasma was used as a substrate for pancreatic kallikrein in vitro and the addition of sulphone caused an inhibition of kinin production, which was dependent on the concentration of...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1969.tb09534.x
更新日期:1969-09-01 00:00:00
abstract::1 The metabolism of extracellular nucleotides plays an important role in nucleotide signalling mediated by P2 receptors. The nucleotide sequence encoding a putative human ecto-ATPase named CD39L1 was reported recently. However, the biological activity of this protein has not been established. 2 Based on the sequence o...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702805
更新日期:1999-09-01 00:00:00
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
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704571
更新日期:2002-03-01 00:00:00
abstract::1. We have investigated pre- and post-junctional responsiveness in vas deferens from wild-type and alpha(2A/D)-adrenoceptor knockout mice. The response to a single stimulus was not significantly different between wild-type and knock-out mice. The isometric contraction to 10 Hz stimulation for 4 s was significantly lar...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704791
更新日期:2002-07-01 00:00:00
abstract::Forty-eight isolated rat hearts were perfused with Krebs solution and with [(3)H]-(-)-noradrenaline ([(3)H]-NA) containing 4.5 nCi/ml in 50 ng/ml, as described by Iversen (1963). To groups of six, cocaine was added to [(3)H]-NA in concentrations of 400 nM, 2 and 10 muM. To the rest Tween 80, 25 mug/ml was added to [(3...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1974.tb10686.x
更新日期:1974-07-01 00:00:00
abstract::The present study examined the ability of the selective imidazoline I(2)-site ligands 2-(-2-benzofuranyl)-2-imidazoline (2-BFI) and 2-[4,5-dihydroimidaz-2-yl]-quinoline (BU224) and selected monoamine oxidase (MAO) inhibitors to evoke locomotor activity in rats bearing a lesion of the nigrostriatal pathway. Male Spragu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0706019
更新日期:2004-12-01 00:00:00
abstract::1 Core and tail skin temperature was measured in rats which had guide cannulae implanted into their brains to allow drug injections directly into the preoptic anterior hypothalamus. 2 Apomorphine and dopamine (10 microgram in 1 microliter) injected into the area of the preoptic anterior hypothalamus caused a fall in c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb09742.x
更新日期:1977-09-01 00:00:00
abstract::1. Chronic treatment with low doses of the selective monoamine oxidase (MAO) type B inhibitors selegiline [(-)-deprenyl] and rasagiline, causes elevation in extracellular level of 3,4-dihydroxyphenylethylamine (dopamine) in the rat striatum in vivo (Lamensdorf et al., 1996). The present study was carried out to determ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702389
更新日期:1999-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:QT prolongation is commonly used as a surrogate marker for Torsade de Pointes (TdP) risk of non-cardiovascular drugs. However, use of this indirect marker often leads to misinterpretation of the realistic TdP risk, as tested compounds may cause QT prolongation without evoking TdP in humans. A neg...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01795.x
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Metabolic and cardiovascular abnormalities accompanying metabolic syndrome, such as obesity, insulin resistance and hypertension, are all associated with endothelial dysfunction and are independent risk factors for erectile dysfunction. The purpose of the present study was to investigate the vasc...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00825.x
更新日期:2010-09-01 00:00:00
abstract::We investigated the effects of cocaine and corticosterone on the noradrenaline-induced relaxation of rat oesophageal smooth muscle in the absence and presence of the selective beta2-antagonist, ICI 111,551. It was found that the concentration-response curve (CRC) of noradrenaline was not shifted by ICI 118,551 at 1 mi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb16396.x
更新日期:1995-10-01 00:00:00
abstract::1. The effects of chronic oral administration of desmethylimipramine (DMI) or zimelidine (1.25 and 5 mg kg-1 twice daily for 21 days) were studied on rat whole cortical gamma-aminobutyric acidB (GABAB) binding sites. No changes in receptor affinity or number were found with either drug. 2. A subsequent study of GABAB ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11438.x
更新日期:1988-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In patients with pulmonary hypertension (PH) associated with lung disease and/or hypoxia (Group III), decreased pulmonary vascular tone and tissue hypoxia is therapeutically beneficial. PGE2 and PGI2 induce potent relaxation of human bronchi from non-PH (control) patients via EP4 and IP receptors...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14854
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Strontium ranelate, a drug approved and until recently used for the treatment of osteoporosis, mediates its effects on bone at least in part via the calcium-sensing (CaS) receptor. However, it is not known whether bone-targeted CaS receptor positive allosteric modulators (PAMs; calcimimetics) rep...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14344
更新日期:2018-11-01 00:00:00
abstract::1. The effect of histamine H1-receptor stimulation on inositol phospholipid hydrolysis has been investigated in the hamster vas deferens smooth muscle cell line, DDT1MF-2. 2. Histamine (EC50 = 27 microM) stimulated the accumulation of [3H]-inositol phosphates in DDT1MF-2 cells prelabelled with [3H]-myo-inositol. 2-Thi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13462.x
更新日期:1993-01-01 00:00:00
abstract::Des-Arg9-bradykinin (des-Arg9-BK) caused endothelium-dependent relaxations in human, isolated coronary arteries which upregulated with in vitro incubation time. Relaxations to des-Arg9-BK were inhibited by the B1 receptor antagonist, des-Arg9-[Leu3]-BK (pK(B), 6.14 +/- 0.11) but were unaffected by the B2 receptor anta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1995.tb15108.x
更新日期:1995-12-01 00:00:00
abstract::1. The present study was aimed at elucidating the apoptosis inhibitory properties of the cyanoguanidine CHS 828. CHS 828 exhibits impressive cytotoxic activity in vitro and in vivo. Apoptosis is not its main mode of cytotoxic effect, and we have previously proposed a dual mechanism, where CHS 828 inhibits its own cell...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0704888
更新日期:2002-10-01 00:00:00
abstract::1. The effect of the myorelaxant drugs baclofen, diazepam and tizanidine have been compared on in vitro preparations of baby rat spinal cord and adult rat superior cervical ganglion. 2. Dorsal root-elicited long duration (time to half decay 9.71 +/- 0.29 s.e. mean, n = 31) ipsilateral ventral root reflexes (DR-VRP), m...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb12794.x
更新日期:1992-10-01 00:00:00
abstract:BACKGROUND AND PURPOSE:In the sensorimotor (SM) and medial prefrontal (mPF) basal ganglia (BG) circuits, the cortical information is transferred to the substantia nigra pars reticulata (SNr) through the hyperdirect trans-subthalamic pathway and through the direct and indirect trans-striatal pathways. The cannabinoid CB...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.14613
更新日期:2019-04-01 00:00:00
abstract::1. Mouse islets were used to define the characteristics and study the mechanisms of the stimulation of insulin release by compound AZ-DF 265, 4-[[N-(alpha-phenyl-2-piperidino-benzyl) carbamoyl]methyl] benzoic acid, a substituted benzoic acid with an asymmetric carbon atom. 2. At a non-stimulatory concentration of gluc...
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
abstract::Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and inhibits stimulated adenylate cyclase. Adenosine 5'-O-(1-thiodiphosphate) (ADP-alpha-S) and adenosine 5'-O-(2-thiodiphosphate) (ADP-beta-S) act at the ADP receptor and achieve the same maximal rate of human platelet aggregation as each other. Adenos...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1982.tb08781.x
更新日期:1982-02-01 00:00:00
abstract::1. The class III antiarrhythmic azimilide has previously been shown to inhibit I(Ks) and I(Kr) in guinea-pig cardiac myocytes and I(Ks) (minK) channels expressed in Xenopus oocytes. Because HERG channels underly the conductance I(Kr), in human heart, the effects of azimilide on HERG channels expressed in Xenopus oocyt...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701575
更新日期:1998-01-01 00:00:00
abstract::Relaxin is a small heterodimeric peptide hormone of the insulin/relaxin superfamily produced mainly in female and male reproductive organs. It has potent antifibrotic, vasodilatory and angiogenic effects and regulates the normal function of various physiological systems. Preclinical studies and recent clinical trials ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.13656
更新日期:2017-05-01 00:00:00
abstract::1. The effects of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) were investigated on evoked and spontaneous currents in freshly-isolated cells from the rat portal vein by use of conventional whole-cell recording and perforated-patch techniques. 2. At a holding potential of -60 mV in potassium-free, caesium-conta...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1996.tb15171.x
更新日期:1996-01-01 00:00:00
abstract::The N6-2'-O-dibutyryl derivative of adenosine 3',5'-monophosphate (db cyclic AMP) and related compounds have been micro-injected into the preoptic/anterior hypothalamic nuclei (PO/AH) of the unanaesthetized, restrained rabbit and the effects on deep body temperature observed. Db cyclic AMP (100-400 micrograms) produce...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16122.x
更新日期:1984-04-01 00:00:00
abstract::1. The potencies of some beta-adrenoreceptor blocking drugs in reducing noradrenaline uptake by the isolated heart were compared with their potencies in reducing the release of noradrenaline from the heart by tyramine.2. Of the drugs tested, propranolol, pronethalol and dichloroisoprenaline were the most potent in blo...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07957.x
更新日期:1968-09-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Subset of macrophages within the atheroma plaque displays a high glucose uptake activity. Nevertheless, the molecular mechanisms and the pathophysiological significance of this high glucose need remain unclear. While the role for hypoxia and hypoxia inducible factor 1α has been demonstrated, the ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.15358
更新日期:2020-12-29 00:00:00
abstract::1. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), gepirone, buspirone and ipsapirone dose-dependently antagonized the head-shakes induced by 1-(2,5-dimethoxy 4-iodophenyl)-2-amino propane hydrochloride (DOI) (1.0 mg kg-1) in mice, when these agents were given i.p. 10 min beforehand. 2. para-Chlorophenylalanine (...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1993.tb13727.x
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Rosiglitazone is an anti-diabetic drug improving insulin sensitivity and glucose uptake in skeletal muscle and adipose tissues. However, several recent clinical trials suggest that rosiglitazone can increase the risk of cardiovascular ischaemia, although other studies failed to show such risks. T...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01539.x
更新日期:2011-12-01 00:00:00
abstract::1. Aqueous extracts of stratum corneum were found to cause histamine-like contractions of the guinea-pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide.2. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, part...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1972.tb09581.x
更新日期:1972-05-01 00:00:00