Abstract：
BACKGROUNDS AND PURPOSE:Lactic acidosis is a fatal adverse effect of metformin, but the risk factor remains unclear. Multidrug and toxin extrusion 1 (MATE1) is expressed in the luminal membrane of the kidney and liver. MATE1 was revealed to be responsible for the tubular and biliary secretion of metformin. Therefore, some MATE polymorphisms, that cause it to function abnormally, are hypothesized to induce lactic acidosis. The purpose of this study is to clarify the association between MATE dysfunction and metformin-induced lactic acidosis. EXPERIMENTAL APPROACH:Blood lactate, pH and bicarbonate ion (HCO(3) (-) ) levels were evaluated during continuous administration of 3 mg·mL(-1) metformin in drinking water using Mate1 knockout (-/-), heterozygous (+/-) and wild-type (+/+) mice. To determine the tissue accumulation of metformin, mice were given 400 mg·kg(-1) metformin orally. Furthermore, blood lactate data were obtained from diabetic patients given metformin. KEY RESULTS:Seven days after metformin administration in drinking water, significantly higher blood lactate, lower pH and HCO(3) (-) levels were observed in Mate1(-/-) mice, but not in Mate1(+/-) mice. The blood lactate levels were not affected in patients with the heterozygous MATE variant (MATE1-L125F, MATE1-G64D, MATE2-K-G211V). Sixty minutes after metformin administration (400 mg·kg(-1) , p.o.) the hepatic concentration of metformin was markedly higher in Mate1(-/-) mice than in Mate1(+/+) mice. CONCLUSION AND IMPLICATIONS:MATE1 dysfunction caused a marked elevation in the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin-induced lactic acidosis.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Toyama K,Yonezawa A,Masuda S,Osawa R,Hosokawa M,Fujimoto S,Inagaki N,Inui K,Katsura Tdoi
10.1111/j.1476-5381.2012.01853.xsubject
Has Abstractpub_date
2012-06-01 00:00:00pages
1183-91issue
3eissn
0007-1188issn
1476-5381journal_volume
166pub_type
杂志文章abstract：:1. In order to characterize the neuropeptide Y (NPY) Y1 receptors known to be present in rabbit isolated vas deferens and saphenous vein, the pharmacological activity of the selective NPY Y1 receptor agonists, [Leu31,Pro34] NPY and various other peptide agonists, together with the putative NPY antagonist, benextramine...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb16311.x
更新日期：1995-05-01 00:00:00
abstract：:1. The tachykinin receptor mediating contraction of the guinea-pig isolated proximal urethra has been characterized by use of receptor selective agonists and antagonists. All experiments were performed in the presence of peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each) in order to reduce peptide...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14430.x
更新日期：1992-08-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Heat-sensitive transient receptor potential vanilloid (TRPV) channels are expressed in various epithelial tissues regulating, among else, barrier functions. Their expression is well established in the distal nephron; however, we have no data about their presence in podocytes. As podocytes are ind...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14052
更新日期：2017-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:The cannabinoid receptor-mediated analgesic effects of 2-arachidonoylglycerol (2-AG) are limited by monoacylglycerol lipase (MAGL). 4-nitrophenyl 4-[bis (1,3-benzodioxol-5-yl) (hydroxy) methyl] piperidine-1-carboxylate (JZL184) is a potent inhibitor of MAGL in the mouse, though potency is reporte...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2012.02179.x
更新日期：2012-12-01 00:00:00
abstract：:1. The cyclic analogue of dopamine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated. 2. When given intraventricularly, ADTN produced so...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1975.tb07416.x
更新日期：1975-05-01 00:00:00
abstract：:1. Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentratio...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb14210.x
更新日期：1992-01-01 00:00:00
abstract：:1 The activity and pulmonary metabolism of two peptides, 7-homo Pro-bradykinin and 8-homo Phe-bradykinin were studied in isolated systems. 2 Both analogues were about 50-70 times less active than bradykinin on the guinea-pig ileum and 70-160 times less active on isolated strips of cat terminal ileum. 3 The action of b...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1977.tb06985.x
更新日期：1977-01-01 00:00:00
abstract：:1. Opioid agonists inhibit neurogenic mucus secretion in the airways. The mechanism of the inhibition is unknown but may be via opening of potassium (K+) channels. We studied the effect on neurogenic secretion in ferret trachea in vitro of the OP1 receptor (formerly known as delta opioid receptor) agonist [D-Pen2,5]en...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701786
更新日期：1998-04-01 00:00:00
abstract：:1. The aim of this study was to characterize the pharmacological profile of the GABA(B1)/GABA(B2) heterodimeric receptor expressed in Chinese hamster ovary (CHO) cells. We have compared receptor binding affinity and functional activity for a series of agonists and antagonists. 2. The chimeric G-protein, G(qi5), was us...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703682
更新日期：2000-11-01 00:00:00
abstract：:Pulmonary arterial hypertension (PAH) is a complex disease characterized by elevated pulmonary arterial pressure, pulmonary vascular remodelling and occlusive pulmonary vascular lesions, leading to right heart failure. Evidence from recent epidemiological studies suggests the influence of gender on the development of ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12281
更新日期：2014-02-01 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
abstract：:The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0702210
更新日期：1998-12-01 00:00:00
abstract：:A dispersed rat anterior pituitary cell system has been used to investigate the effects of cyproheptadine and metergoline on prolactin secretion. Both drugs were potent inhibitors of prolactin secretion. However, the inhibition was not antagonized by either 5-hydroxytryptamine or a variety of dopamine antagonists. We ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1980.tb10896.x
更新日期：1980-09-01 00:00:00
abstract：:1. Two preparations, a segment of the ileum and the myenteric plexuslongitudinal muscle preparation, have been used for an analysis of the inhibitory effects of adrenaline, noradrenaline and isoprenaline on the contractor responses of the longitudinal muscle to acetylcholine or to electrical, coaxial or field, stimula...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1970.tb12903.x
更新日期：1970-06-01 00:00:00
abstract：:1. In the present study, we describe the expression of the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as well as their receptors in PC-3 cells, a human prostate cancer cell line. In addition, we have investigated their role in apoptosis induced by s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705317
更新日期：2003-07-01 00:00:00
abstract：:The cardiovascular effects of doxazosin, a quinazoline derivative related to prasozin were investigated and compared to prazosin in the rabbit. Radioligand binding studies using rabbit cerebral membranes showed that both doxazosin and prazosin were roughly equipotent at displacing [3H]-prazosin from specific binding s...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1985.tb09437.x
更新日期：1985-09-01 00:00:00
abstract：:Rodent models of chronic pain may elucidate pathophysiological mechanisms and identify potential drug targets, but whether they predict clinical efficacy of novel compounds is controversial. Several potential analgesics have failed in clinical trials, in spite of strong animal modelling support for efficacy, but there...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/j.1476-5381.2011.01300.x
更新日期：2011-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:While remifentanil can be used either during labour or fetal surgery, more should be known about the transplacental transfer of this opioid. The aim of this study was to investigate the placental transfer and haemodynamic effects of remifentanil after i.v. administration to pregnant ewes. EXPERI...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2010.00783.x
更新日期：2010-12-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Early soluble epoxide hydrolase inhibitors (sEHIs) such as 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) are effective anti-hypertensive and anti-inflammatory agents in various animal models. However, their poor metabolic stability and limited water solubility make them difficult to use pha...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.2008.00009.x
更新日期：2009-01-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Abdominal aortic aneurysm (AAA) is a degenerative disease with irreversible and progressive dilation of the artery. But there are few options for efficacious treatment except for traditional surgery. Probucol has been widely applied to treat hyperlipidaemia and atherosclerosis in clinic, but whet...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14857
更新日期：2020-01-01 00:00:00
abstract：:1. The pharmacokinetic interaction between phenylbutazone and sulphadoxine has been studied in live sheep.2. Intravenous injection of phenylbutazone causes a rapid fall in the concentration of total sulphadoxine together with a simultaneous rise in the concentration of free sulphadoxine in plasma. Both processes are c...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1971-10-01 00:00:00
abstract：:Nociceptin (NC), alias Orphanin FQ, has been recently identified as the endogenous ligand of the opioid receptor-like 1 receptor (OP(4)). This new NC/OP(4) receptor system belongs to the opioid family and has been characterized pharmacologically with functional and binding assays on native (mouse, rat, guinea-pig) and...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1038/sj.bjp.0703219
更新日期：2000-04-01 00:00:00
abstract：:1. The effects of different K+ channel blockers were studied on nitric oxide (NO)-mediated non-adrenergic non-cholinergic (NANC) relaxations in the canine ileocolonic junction. 2. The non-selective blockers of K+ channels, 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the blocker of large conductance Ca(2+)-...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1993.tb13847.x
更新日期：1993-10-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Botulinum toxin type A (BoNT/A) injections into hyperactive muscles provide effective treatment for spasticity and dystonias, presumably due to its local effects on extrafusal and intrafusal motor fibres. A recent discovery of toxin's retrograde axonal transport to CNS might suggest additional ac...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.14846
更新日期：2020-01-01 00:00:00
abstract：:Rabbits treated with 2-deoxy-D-glucose (2DG) (300 mg/kg) show an increased intake of food and water. Pretreatment with haloperidol (1 mg/kg) abolishes the increase in water intake but does not prevent the increase in food intake. ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：
更新日期：1979-05-01 00:00:00
abstract：:1 Thermic oedema induced by heating rat paws at 46.5 degrees C was potentiated by local injection of adrenaline, noradrenaline or high doses of isoprenaline. The pro-inflammatory effect of sympathomimetic amines was antagonized by phenoxybenzamine or phentolamine but not by propranolol.2 The subcutaneous space of heat...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1974.tb08568.x
更新日期：1974-02-01 00:00:00
abstract：BACKGROUND AND PURPOSE:An innovative chemical approach, named peptide welding technology (PWT), allows the synthesis of multibranched peptides with extraordinary high yield, purity and reproducibility. With this approach, three different tetrabranched derivatives of nociceptin/orphanin FQ (N/OFQ) have been synthesized ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/bph.12799
更新日期：2014-09-01 00:00:00
abstract：:1. Pharmacological inhibitors of protein kinase A (PKA) and protein phosphatases 1/2A were used to determine whether basal L-type Ca(2+) current (I(Ca)) observed in the absence of exogenous beta-adrenergic receptor stimulation is sustained by PKA-mediated phosphorylation. Amphotericin B was used to record whole-cell I...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706809
更新日期：2006-08-01 00:00:00
abstract：:1. The role of nitic oxide (NO) derived from L-arginine in the regional vasodilator effects of endothelin-1 has been investigated in anaesthetized, spontaneously hypertensive (SH) rats in which autonomic reflexes were abolished by ganglion blockade. The experimental design incorporated animals infused with phenylephri...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1992.tb09049.x
更新日期：1992-03-01 00:00:00
abstract：:1 New 2H-1,4-benzoxazine derivatives were synthesized and tested for their agonist properties on the ATP-sensitive K(+) channels (K(ATP)) of native rat skeletal muscle fibres by using the patch-clamp technique. The novel modifications involved the introduction at position 2 of the benzoxazine ring of alkyl substituent...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705233
更新日期：2003-05-01 00:00:00
