Abstract:
BACKGROUND AND PURPOSE:Pancreatic islet transplantation is a promising therapeutic approach for Type 1 diabetes. A major prerequisite for the survival of grafted islets is a rapid revascularization after transplantation. Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to promote angiogenesis. Therefore, we investigated in this study whether EPO improves the revascularization of transplanted islets. EXPERIMENTAL APPROACH:Islets from FVB/N mice were transplanted into dorsal skinfold chambers of recipient animals, which were daily treated with an intraperitoneal injection of EPO (500 IU·kg-1 ) or vehicle (control) throughout an observation period of 14 days. In a second set of experiments, animals were only pretreated with EPO over a 6-day period prior to islet transplantation. The revascularization of the grafts was assessed by repetitive intravital fluorescence microscopy and immunohistochemistry. In addition, a streptozotocin-induced diabetic mouse model was used to study the effect of EPO-pretreatment on the endocrine function of the grafts. KEY RESULTS:EPO treatment slightly accelerated the revascularization of the islet grafts. This effect was markedly more pronounced in EPO-pretreated animals, resulting in significantly higher numbers of engrafted islets and an improved perfusion of endocrine tissue without affecting systemic haematocrit levels when compared with controls. Moreover, EPO-pretreatment significantly accelerated the recovery of normoglycaemia in diabetic mice after islet transplantation. CONCLUSION AND IMPLICATIONS:These findings demonstrate that, particularly, short-term EPO-pretreatment represents a promising therapeutic approach to improve the outcome of islet transplantation, without an increased risk of thromboembolic events.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Menger MM,Nalbach L,Roma LP,Körbel C,Wrublewsky S,Glanemann M,Laschke MW,Menger MD,Ampofo Edoi
10.1111/bph.14925subject
Has Abstractpub_date
2020-04-01 00:00:00pages
1651-1665issue
7eissn
0007-1188issn
1476-5381journal_volume
177pub_type
杂志文章abstract::1. Muscularis mucosae of the distal oesophagus of the opossum contracts in response to substance P and to a variety of tachykinins. To delineate the nature of the receptors present in this tissue, we evaluated contractile responses to substance P, neurokinin A, neurokinin B, eledoisin and analogues believed to be high...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1989.tb12556.x
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND AND PURPOSE:It is well known that adenine-based purines exert multiple effects on pain transmission. However, less attention has been given to the potential effects of guanine-based purines on pain transmission. The aim of this study was to investigate the effects of intraperitoneal (i.p.) and oral (p.o.) ad...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2009.00597.x
更新日期:2010-03-01 00:00:00
abstract::1 Burimamide injected intravenously in the anaesthetized or conscious cat produced significant increases in gastric acid secretion: in the anaesthetized cat it produced increased gastric mucosal blood flow. 2 Metiamide, in doses which inhibited pentagastrin-stimulated acid secretion, produced no increase in gastric ac...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1975.tb07361.x
更新日期:1975-02-01 00:00:00
abstract:BACKGROUND AND PURPOSE:5-Hydroxytryptamine (5-HT) has been shown to control and modulate many physiological and behavioural functions in insects. In this study, we report the cloning and pharmacological properties of a 5-HT(1) receptor of an insect model for neurobiology, physiology and pharmacology. EXPERIMENTAL APPR...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2010.00638.x
更新日期:2010-04-01 00:00:00
abstract::1. Several amino-acid esters and amides have been prepared and their toxicological and pharmacological properties have been investigated. Some of the quaternary esters and amides were lethal to mice at doses below 1 mg/kg; this lethality was usually associated with high nicotinic activity. None of the compounds showed...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1968.tb07056.x
更新日期:1968-10-01 00:00:00
abstract::The effects of infusions of eicosapentaenoic acid (EPA) (6 X 10(-8) mol min-1 and 15 X 10(-8) mol min-1) on the coronary constriction and the release of immunoreactive sulphidopeptide-leukotrienes (SP-LT), thromboxane B2(TXB2) and 6-keto-prostaglandin F1 alpha (PGF1 alpha) from perfused anaphylactic guinea-pig hearts ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1987.tb08961.x
更新日期:1987-02-01 00:00:00
abstract::1. CS-747 is a novel thienopyridine-type platelet ADP inhibitor which lacks in vitro activity. This study examined pharmacological profiles of R-99224, a hepatic metabolite of CS-747. 2. R-99224 produced a concentration-dependent inhibition of in vitro platelet aggregation in washed human platelets (0.03 - 1 microg ml...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703761
更新日期:2001-01-01 00:00:00
abstract::ST-segment elevation following temporary coronary artery occlusion was measured from nine epicardial leads in open-chest anaesthetized dogs. This was greatly reduced by the prior administration of the anti-dysrhythmic aminosteroid, ORG 6001. It is suggested that this effect is related either to a reduction in the exte...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb08421.x
更新日期:1977-10-01 00:00:00
abstract::AMPA-type glutamate receptors are one of the most dynamic components of excitatory synapses. Their regulated addition and removal from synapses leads to long-lasting forms of synaptic plasticity, known as long-term potentiation (LTP) and long-term depression (LTD). In addition, AMPA receptors reach their synaptic targ...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1038/sj.bjp.0707525
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abstract::Immersion of the hind paws of anesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45 degrees C, a maximal response was obtained between 55 degrees C and 60...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1984.tb16461.x
更新日期:1984-05-01 00:00:00
abstract:BACKGROUND AND PURPOSE:We have developed a strategy to target the permanently charged lidocaine derivative lidocaine N-ethyl bromide (QX-314) selectively into nociceptive sensory neurons through the large-pore transient receptor potential cation channel subfamily V (TRPV1) noxious heat detector channel. This involves c...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.2011.01391.x
更新日期:2011-09-01 00:00:00
abstract::Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro-inflammatory settings and clinical trials to treat idiopathic pulmonar...
journal_title:British journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1111/bph.15248
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abstract::We investigated the rate of penetration into and the intra-relationship between the serum, cerebrospinal fluid (CSF) and regional brain extracellular fluid (bECF) compartments following systemic administration of lamotrigine in rat. The serum pharmacokinetics were biphasic with an initial distribution phase, (half-lif...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0703337
更新日期:2000-05-01 00:00:00
abstract::Aspirin at therapeutic concentrations does not inhibit the uptake of 5-hydroxytryptamine (5-HT) by blood platelets nor induce release of 5-HT from platelets, although platelet aggregation responses to collagen and arachidonic acid (which are dependent on platelet prostaglandin synthesis) are abolished. This does not s...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1977.tb07735.x
更新日期:1977-04-01 00:00:00
abstract::1. The similarity in molecular structure between the histamine H2-agonist dimaprit (3-dimethylamino-propyl-isothiourea) and the endogenous nitric oxide synthase (NOS) substrate L-arginine prompted us to study the effect of dimaprit and some dimaprit analogues on NOS activity. Dimaprit and some of its analogues were te...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0702552
更新日期:1999-05-01 00:00:00
abstract::Human foetal small intestine was shown to contain both alpha- and beta-adrenoceptors with a predominance of beta-adrenoceptors. The tissue examined was obtained from foetuses of gestational age between 8 and 26 weeks. ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1971.tb08055.x
更新日期:1971-03-01 00:00:00
abstract::1. The effects of drugs and altering stimulus parameters on neurogenic responses to electrical field stimulation (EFS) have been investigated in distal and proximal portions of the guinea-pig trachea. 2. In the presence of indomethacin (3 microM) and propranolol (1 microM) two contractile phases were evident in both t...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1990.tb14174.x
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Ajmaline is a widely used antiarrhythmic drug. Its action on voltage-gated ion channels in skeletal muscle is not well documented and we have here elucidated its effects on Na(+) and K(+) channels. EXPERIMENTAL APPROACH:Sodium (I(Na)) and potassium (I(K)) currents in amphibian skeletal muscle fi...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0707194
更新日期:2007-05-01 00:00:00
abstract::1 The effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin-dispersed cat adrenocortical cells were investigated. 2 Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)-evoked prostaglandin and steroid release, whereas higher concentratio...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb07477.x
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abstract::1 The effects of pretreatment with aspirin, and of prostacyclin (PGI(2)) infusions, on responses to myocardial ischaemia and infarction produced by ligation of a coronary artery were investigated in conscious rats.2 Surgical preparation, under halothane anaesthesia, consisted of implanting exteriorized aortic and jugu...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1983.tb09359.x
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journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1980.tb14561.x
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abstract::The S-S reducing agent, dithiothreitol (DTT) altered the properties of nicotinic receptors in rat superior cervical ganglia such that (i) carbachol became less active as a depolarizing agent and (ii) bromo-acetylcholine produced an irreversible depolarization. The latter was temporarily annulled by hexamethonium (whic...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1976.tb06968.x
更新日期:1976-01-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Idiopathic pulmonary fibrosis (IPF) is a progressive fibro-proliferative disorder refractory to current therapy commonly complicated by the development of pulmonary hypertension (PH); the associated morbidity and mortality are substantial. Natriuretic peptides possess vasodilator and anti-fibroti...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:2014-07-01 00:00:00
abstract::1. It has previously been shown that the hypoglycaemic drug (-)-AZ-DF-265 stimulates insulin release from mouse islets; in the presence of 3 mM glucose it also inhibits 86Rb-efflux from 86Rb-loaded islets. Based on these data we tested the hypothesis that (-)-AZ-DF-265 inhibits ATP-sensitive potassium channels. 2. We ...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1992.tb14324.x
更新日期:1992-06-01 00:00:00
abstract::1. The aim of this study was to determine the response of porcine small pulmonary arteries to intralumenal flow and to identify the cellular mechanisms and potential mediators involved in the response. 2. Porcine small pulmonary arteries were isolated from a branch of the main intrapulmonary artery of the lower lung l...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1038/sj.bjp.0701846
更新日期:1998-05-01 00:00:00
abstract::1. The influence of the thromboxane A2-mimetic U46619 (11 alpha, 9 alpha-epoxymethano PGH2) on 5-hydroxy-tryptamine (5-HT)-induced contractions of the rabbit isolated femoral artery has been examined. 2. In the absence of U46619, 5-HT responses were mediated predominantly by 5-HT2-receptors as judged by potent, surmou...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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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...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1988.tb11637.x
更新日期:1988-08-01 00:00:00
abstract::1. In anaesthetized patients under controlled respiration, samples of lumbar cerebrospinal fluid were withdrawn 15 and 60 min after an intravenous injection of 30 mg tubocurarine. When tested on the frog rectus muscle preparation contracted by acetylcholine, they exerted curare-like activity which corresponded to betw...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/j.1476-5381.1973.tb08206.x
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abstract::1. The aim of this study was to investigate the cardiovascular effects of a novel, potent and specific phosphodiesterase 5 (PDE 5) inhibitor, 1,3 dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl)-pyrazolo[3,4-d]pyrimidin-4-(5H)-one (DMPPO) in phenylephrine-precontracted rat aortic rings and different in vivo rat p...
journal_title:British journal of pharmacology
pub_type: 杂志文章
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更新日期:1996-07-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Bleomycin (BLM), one of the most common sclerosants, is often used to treat venous malformations (VMs). The present study was designed to investigate whether endothelial mesenchymal transition (EndoMT) contributes to the therapeutic effects of BLM. EXPERIMENTAL APPROACH:Endothelial and mesenchym...
journal_title:British journal of pharmacology
pub_type: 杂志文章
doi:10.1111/bph.12355
更新日期:2013-11-01 00:00:00