Abstract:
:Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-based S1P-containing microparticles (PLGA-S1P), which are biodegradable and continuously release S1P, and studied the effects of PLGA-S1P on neovascularization in murine ischemic hindlimbs. Intramuscular injections of PLGA-S1P stimulated blood flow in C57BL/6 mice dose-dependently, with repeated administrations at a 3-day interval, rather than a single bolus or 6-day interval, over 28 days conferring the optimal stimulating effect. In Balb/c mice that exhibit limb necrosis and dysfunction due to retarded blood flow recovery, injections of PLGA-S1P stimulated blood flow with alleviation of limb necrosis and dysfunction. PLGA-S1P alone did not induce edema in ischemic limbs, and rather blocked vascular endothelial growth factor-induced edema. PLGA-S1P not only increased the microvessel densities in ischemic muscle, but promoted coverage of vessels with smooth muscle cells and pericytes, thus stabilizing vessels. PLGA-S1P stimulated Akt and ERK with increased phosphorylation of endothelial nitric oxide synthase in ischemic muscle. The effects of the nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methylester, showed that PLGA-S1P-induced blood flow stimulation was partially dependent on nitric oxide. Injections of PLGA-S1P also increased the expression of angiogenic factors and the recruitment of CD45-, CD11b- and Gr-1-positive myeloid cells, which are implicated in post-ischemic angiogenesis, into ischemic muscle. These results indicate that PLGA-based, sustained local delivery of S1P is a potentially useful therapeutic modality for stimulating post-ischemic angiogenesis.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Qi X,Okamoto Y,Murakawa T,Wang F,Oyama O,Ohkawa R,Yoshioka K,Du W,Sugimoto N,Yatomi Y,Takuwa N,Takuwa Ydoi
10.1016/j.ejphar.2010.02.038subject
Has Abstractpub_date
2010-05-25 00:00:00pages
121-31issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(10)00161-5journal_volume
634pub_type
杂志文章abstract::The effect of nimodipine was studied on EEG power density spectra as well as on 31P-NMR spectra of the brain before, during and after four-vessel occlusion (FVO) in the restrained conscious rat. EEG-spectral analysis: eight rats were submitted to 5 min FVO and four of them received nimodipine (1 mg/kg orally) 75 min b...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90799-5
更新日期:1986-06-24 00:00:00
abstract::Little information is available on the influence of sex in combination with smoking habits and combined oral contraceptives (COC) use on cellular inflammatory indexes such as neutrophil/lymphocyte ratio (NLR), derived NRL (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), mean platelet volume/pl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173762
更新日期:2021-01-15 00:00:00
abstract::The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg x kg(-1), i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01008-1
更新日期:2001-05-25 00:00:00
abstract::Airway responsiveness to histamine, substance P, methacholine and bilateral electrical vagal stimulation was assessed in capsaicin-treated and control guinea pigs. In animals treated with capsaicin (50 mg/kg s.c.) 7 days before experiments, airway responsiveness to histamine, substance P and vagal stimulation was sign...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90148-y
更新日期:1990-01-03 00:00:00
abstract::Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress-sensitive Ca2+-permeable channel. The activation of TRPM2 by H2O2 causes cell death in various types of cells. 5-Fluorouracil (5-FU) is an important anticancer drug, but myelosuppression is one of the most frequent adverse effects. The involvemen...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2020.173671
更新日期:2021-01-15 00:00:00
abstract::Cocaine and a cocaine analog, WIN 36,065-2, were administered daily for 3 or 4 days. Both compounds developed sensitization to their locomotor stimulatory effects, with similarly shaped dose-response curves. Dosages giving optimal sensitization were 25 mg/kg per day for cocaine and 3 mg/kg for WIN 35,065-2. At 40 mg/k...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(86)90184-6
更新日期:1986-10-14 00:00:00
abstract::The 8-substituted 9-ethyladenine derivatives: 8-bromo-9-ethyladenine (ANR 82), 8-ethoxy- 9-ethyladenine (ANR 94), and 8-furyl-9-ethyladenine (ANR 152) have been characterized in vitro as adenosine receptor antagonists. Adenosine is deeply involved in the control of motor behaviour and substantial evidences indicate th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.01.057
更新日期:2005-04-11 00:00:00
abstract::We examined whether the proteinase-activated receptor-2 (PAR2) agonist, H-Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SLIGRL-NH2), could induce scratching behavior in mice. Intradermal injections of SLIGRL-NH2 (10-50 microg) evoked dose dependent scratching. This behavior peaked near 5 min and returned to preinjection levels within ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.11.012
更新日期:2006-01-20 00:00:00
abstract::Iloperidone (HP 873; 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy] -3- methoxyphenyl]ethanone) is a compound currently in clinical trials for the treatment of schizophrenia. Iloperidone displays affinity for dopamine D2 receptors and for 5-HT2A receptors and has a variety of in vivo activities sug...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(96)00840-0
更新日期:1996-12-19 00:00:00
abstract::Stimulation of muscarinic M1-receptors in isolated rabbit vas deferens by McN-A-343 inhibited electrically induced twitch contractions susceptible to competitive blockade by (+)-, (+/-), (-)-telenzepine and pirenzepine (pA2 = 9.12, 8.86, 6.98 and 7.79, respectively). The inhibition of twitch contractions by 10(-6) M M...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90604-5
更新日期:1990-05-03 00:00:00
abstract::The pharmacological characteristics of the binding of [3H]8-OH-DPAT ([3H]8-hydroxy-2(di-n-propylamino)tetralin, [125I]CYP ((-)[125I]iodocyanopindolol) (in the presence of 30 microM (-)isoprenaline) and [3H]mesulergine to 5-HT1 recognition sites were studied in rat and pig brain membranes. [3H]8-OH-DPAT bound in rat an...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(85)90658-2
更新日期:1985-11-26 00:00:00
abstract::In rat thoracic aorta, contractile responses to arginine vasopressin are two-fold higher in females than in males. To determine the roles of extracellular and intracellular Ca2+ in this sexual dimorphism in vascular function, vascular reactivity and Ca2+ channel function were examined in thoracic aortae of male and fe...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00700-6
更新日期:1998-11-20 00:00:00
abstract::G protein-coupled receptors (GPCRs) are a family of membrane receptors that regulate physiology and pathology of various organs. Consequently, about 40% of drugs in the market targets GPCRs. Heterotrimeric G proteins are composed of α, β, and γ subunits, and act as the key downstream signaling molecules of GPCRs. The ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2015.05.016
更新日期:2015-09-15 00:00:00
abstract::To evaluate the possible role of 5-HT 1A and 5-HT 2A receptors in the anticonvulsant effect of swim stress, mice were pre-treated with agonists and antagonists of these receptors prior to exposure to stress and the intravenous infusion of picrotoxin. 8-OH-DPAT ((+/-)-8-hydroxy-2-(di-n-propylamino) tetralin) and WAY-10...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.10.021
更新日期:2005-12-19 00:00:00
abstract::Inhibition of intrathecal substance P-elicited behavior by mu-, delta- and kappa-opioids was compared. In both the substance P behavioral test and the tail flick antinociceptive test, intrathecal [D-Ala2, Met5]enkephalinamide and [D-Ala2, D-Leu5]enkephalin (DADL) were equipotent, morphine and ethylketazocine were less...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90403-4
更新日期:1982-12-17 00:00:00
abstract::The main purpose of this study was to compare in vitro pharmacological properties of human αCGRP (CGRP) and a recently discovered metabolically stable CGRP analogue, SAX, in isolated rat and human artery segments. In rat, CGRP and SAX induced similar vasodilatory responses in isolated mesenteric artery with the potenc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.04.007
更新日期:2018-06-15 00:00:00
abstract::Calcitonin can selectively modulate the effects of opioids on the rat hypothalamic-pituitary-adrenal axis and increase the release of corticosterone induced by a kappa-opioid receptor agonist. Considerable evidence supports the involvement of opioid and serotonergic systems in the analgesic effect of calcitonin. In th...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01355-1
更新日期:1997-12-04 00:00:00
abstract::The effects of nicotine, carbachol, hexamethonium and scopolamine were investigated on distress vocalizations (DBs) of acutely isolated domestic chicks. Nicotine attenuated, while the antimuscarinic scopolamine increased the frequency of separation-induced DVs. Furthermore, the stress attenuating effects of nicotine w...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90283-1
更新日期:1981-06-19 00:00:00
abstract::The use of antipsychotic medication has consistently been associated with serious side effects including weight gain and metabolic abnormalities. Strategies for mitigating these side effects have been tested, yet effective interventions have not been identified. The current study tested whether two recently identified...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.01.019
更新日期:2011-03-25 00:00:00
abstract::We sought to examine the involvement of central cannabinoid CB2 receptor activation in modulating mechanical allodynia in a mouse model of neuropathic pain. JWH133 was demonstrated to be a selective cannabinoid CB2 receptor agonist in mice, reducing forskolin-stimulated cAMP production in CHO cells expressing mouse ca...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.01.010
更新日期:2008-03-31 00:00:00
abstract::The action of calcitonin gene-related peptide (CGRP) on the vasodepressor response to adenosine was investigated in anesthetized rats. I.v. bolus injections of adenosine (1-100 microg/kg), acetylcholine (0.05-0.4 microg/kg), isoproterenol (1-30 ng/kg), nitroglycerin (0.3-10 microg/kg) and diltiazem (10-300 microg/kg) ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01566-5
更新日期:1998-03-05 00:00:00
abstract::The aim of the research was to characterize muscarinic receptors of bovine ciliary muscle and to investigate the desensitization process. The role of protein kinase C was analyzed. The results show that muscarinic receptors of bovine ciliary muscle have the pharmacological characteristics of the M3 subtype. Acute expo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)10122-4
更新日期:1997-07-09 00:00:00
abstract::Interleukin-1 beta stimulates corticotropin-releasing factor (CRF) secretion from the hypothalamus involving the activation of prostaglandins. This study investigated the possibility that nitric oxide (NO) acts as a mediator of interleukin-1-induced CRF release. An in vitro rat hypothalami continuous perifusion system...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00700-h
更新日期:1995-02-14 00:00:00
abstract::Excitotoxicity and imbalance of sodium and calcium homeostasis trigger pathophysiologic processes in cerebral ischemia which can accelerate neuronal death. Neuroprotective role of cannabidiol (CBD), one of the main non-psychoactive phytocannabinoids of the cannabis plant, has attracted attention of many researchers in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.11.011
更新日期:2017-01-05 00:00:00
abstract::We have examined the effects of the recently described heptadecapeptide nocistatin on K+-evoked glutamate release from rat cerebrocortical slices in vitro. In vivo, nocistatin reverses the action of nociceptin. Nocistatin (100 nM, n = 7) did not inhibit K+-evoked glutamate release alone. Nociceptin (100 nM) inhibited ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(98)00545-7
更新日期:1998-09-04 00:00:00
abstract::The responsiveness of the rat striatal dopamine (DA) receptor system to apomorphine (APO) was assessed after 10 days of antidepressant administration. Desipramine (DMI), dothiepin (DOTH), iprindole (IPR) and nomifensine (NOM) were administered intra-peritoneally, twice daily, to rats for 10 days and 42 h after the las...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90617-4
更新日期:1984-10-15 00:00:00
abstract::Topoisomerase I (Top1) is the specific target of the anticancer drug camptothecin (CPT) that interferes with enzyme activity promoting Top1-mediated DNA breaks and inhibition of DNA and RNA synthesis. To define the specific transcriptional response to CPT, we have determined the CPT-altered transcription profiles in y...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.12.002
更新日期:2009-01-28 00:00:00
abstract::The GABA uptake inhibitor, L-2,4-diaminobutyric acid (L-DABA) was examined for potential anticonvulsant activity in mice. Given intracerebroventricularly (i.c.v., 2 mumoles) L-DABA almost doubled the CD50 of picrotoxin and 3-mercaptopropionate (3-MP), a glutamate decarboxylase inhibitor--the convulsants being administ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(78)90280-7
更新日期:1978-12-01 00:00:00
abstract::Adenosine 5'-triphosphate (ATP), beta, gamma-methylene ATP and alpha, beta-methylene ATP produced relaxation of carbachol-precontracted isolated trachealis muscle from the guinea-pig in the presence of indomethacin (2.8 microM) and the adenosine uptake inhibitor S-(4-nitrobenzyl)-6-thioinosine (NBTI; 300 nM). The pote...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00237-3
更新日期:1996-06-27 00:00:00
abstract::The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathologi...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0014-2999(01)00755-5
更新日期:2001-02-23 00:00:00