Abstract：
BACKGROUND AND PURPOSE:There is growing evidence that inflammation plays a major role in the pathogenesis of neural damage caused by deposition of amyloid β (Aβ) in the brain. Nimodipine has received attention as a drug that might improve learning and reduce cognitive deficits in Alzheimer's disease, but the mechanism of action is poorly known. In this study, we tested the hypothesis that nimodipine inhibited Aβ-stimulated IL-1β release from microglia. EXPERIMENTAL APPROACH:Cultures of N13 microglia cells or primary mouse microglia were treated with nimodipine, and intracellular accumulation and release of IL-1β in response to Aβ or to the P2 receptor agonists ATP and benzoyl ATP (BzATP) were measured. Accumulation of IL-1β was measured in vivo after intrahippocampal inoculation of Aβ in the absence or presence of nimodipine. The effect of nimodipine on Aβ-triggered cytotoxicity was also investigated. KEY RESULTS:We show here that nimodipine dose-dependently inhibited Aβ-stimulated IL-1β synthesis and release from primary microglia and microglia cell lines. Furthermore, nimodipine also inhibited Aβ-induced IL-1βin vivo accumulation at concentrations known to be reached in the CNS. Finally, nimodipine protected microglia from Aβ-dependent cytotoxicity. CONCLUSION AND IMPLICATIONS:These data suggest that alleviation of symptoms of Alzheimer's disease following nimodipine administration might be due to an anti-inflammatory effect and point to a novel role for nimodipine as a centrally acting anti-inflammatory drug.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Sanz JM,Chiozzi P,Colaianna M,Zotti M,Ferrari D,Trabace L,Zuliani G,Di Virgilio Fdoi
10.1111/j.1476-5381.2012.02112.xsubject
Has Abstractpub_date
2012-12-01 00:00:00pages
1702-11issue
8eissn
0007-1188issn
1476-5381journal_volume
167pub_type
杂志文章abstract：:1. The benzodiazepine site of the alpha 6 beta 2 gamma 2 subtype of gamma-aminobutyric acidA (GABAA) receptors is distinguishable from that of the alpha 1 beta 2 gamma 2 subtype by its inability to interact with classical benzodiazepines (i.e., diazepam) and its agonistic response to Ro 15-1788, which behaves as an an...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700931
更新日期：1997-02-01 00:00:00
abstract：:In the rabbit isolated pulmonary artery, neither the ETA receptor antagonist, BQ-123 (10 microM), nor the ETB receptor antagonist, BQ-788 (10 microM), inhibited the contractions induced by 1 nM endothelin-1 (ET-1). However, the combination of BQ-123 and BQ-788 completely inhibited the ET-1-induced contraction. In cont...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb16901.x
更新日期：1994-10-01 00:00:00
abstract：:Binding of the 5-HT(7) receptor antagonist radioligand [(3)H]-SB-269970 to human 5-HT(7(a)) receptors expressed in HEK293 cell membranes (h5-HT(7(a))/293) and to guinea-pig cerebral cortex membranes, was characterized and compared with [(3)H]-5-CT binding. [(3)H]-SB-269970 (1 nM) showed full association with h5-HT(7(a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0703318
更新日期：2000-05-01 00:00:00
abstract：:Recent advances have improved our understanding of the renin-angiotensin system (RAS). These have included the recognition that angiotensin (Ang)-(1-7) is a biologically active product of the RAS cascade. The identification of the ACE homologue ACE2, which forms Ang-(1-7) from Ang II, and the GPCR Mas as an Ang-(1-7) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bph.12159
更新日期：2013-06-01 00:00:00
abstract：:The platelet-lowering drug anagrelide inhibits bone marrow megakaryocytopoiesis by an unknown mechanism. Recently, it was found that anagrelide is bio-transformed in humans into two major metabolites (6,7-dichloro-3-hydroxy-1,5 dihydro-imidazo[2,1-b]quinazolin-2-one (BCH24426) and 2-amino-5,6-dichloro-3,4,-dihydroquin...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706341
更新日期：2005-10-01 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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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1987.tb09004.x
更新日期：1987-05-01 00:00:00
abstract：:1. The effects of capsaicin on voltage-gated Ca2+ currents (ICa), and intracellular Ca2+ concentrations [( Ca2+]i) in cultured dorsal root ganglion (DRG) neurones of the rat were examined in vitro by use of combined patch clamp-microfluorometric recordings. 2. Under voltage-clamp conditions, capsaicin (0.1-10 microM) ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1990.tb12725.x
更新日期：1990-10-01 00:00:00
abstract：:1 Contractions of the cat nictitating membrane were elicited on stimulation of the internal carotid nerve, and the effects were studied of desipramine and two inhibitors of catechol-O-methyltransferase, U-0521 and pyrogallol, on the subsequent relaxation of the muscle. 2 The relaxation of the nictitating membrane occu...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1978.tb07762.x
更新日期：1978-04-01 00:00:00
abstract：:1. The possible involvement of nitric oxide (NO) in the induction and expression of morphine tolerance and dependence was studied in mice. A two-day repeated injection regimen was used to induce morphine tolerance and dependence. Tolerance was assessed by the tail flick test and physical dependence by naloxone challen...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1996.tb15280.x
更新日期：1996-03-01 00:00:00
abstract：:1. The pharmacological features of rat white adipocyte beta-adrenoceptor subtypes were investigated by saturation and beta-agonist competition studies with [3H]-CGP 12177 and by lipolysis induced by beta-agonists as well as their inhibition by CGP 20712A (selective beta 1-antagonist) and ICI 118551 (selective beta 2-a...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700885
更新日期：1997-01-01 00:00:00
abstract：:1. Recently we and others have demonstrated a stereoselective inhibition of slowly activating human I(Ks) (KCNQ1/MinK) and homomeric KCNQ1 potassium channels by the enantiomers of the chromanol 293B. Here, we further characterized the mechanism of the 293B block and studied the influence of the 293B enantiomers on the...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0704421
更新日期：2001-12-01 00:00:00
abstract：:1. The role of adenosine 3':5'-cyclic monophosphate (cyclic AMP) in the regulation of catecholamine (CA) secretion in chromaffin cells remains equivocal from previous studies. 2. In the present study the effect of this cyclic nucleotide on basal CA secretion, as well as on intracellular calcium and membrane potential ...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1995.tb13257.x
更新日期：1995-01-01 00:00:00
abstract：:1. Series of analogues of acetylcholine have been prepared in which the acetyl group was replaced by phenylacetyl, cyclohexylacetyl, diphenylacetyl, dicyclohexylacetyl, (+/-)-phenylcyclohexylacetyl, benziloyl and (+/-)-phenylcyclohexylhydroxyacetyl groups and the trimethylammonium group was replaced by Me(2)EtN(+), Me...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09539.x
更新日期：1969-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1969-09-01 00:00:00
abstract：BACKGROUND AND PURPOSE:Melanin-concentrating hormone receptor 1 (MCH1 receptor) antagonists are being considered as anti-obesity agents. The present study reports a new class of MCH1 receptor antagonists with an 8-methylquinoline scaffold. The molecular mechanism of MCH1 receptor blockade by these antagonists was exami...
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pub_type： 杂志文章
doi：10.1111/bph.12529
更新日期：2014-03-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1989.tb11893.x
更新日期：1989-04-01 00:00:00
abstract：:We synthesized a small-molecule opioid receptor-like 1 (ORL1) receptor agonist, 2-{3-[1-((1R)-acenaphthen-1-yl)piperidin-4-yl]-2,3-dihydro-2-oxo-benzimidazol-1-yl}-N-methylacetamide (W-212393), and investigated its effect on the circadian body temperature rhythm of rats. W-212393 has high affinity for ORL1 receptors i...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0706311
更新日期：2005-09-01 00:00:00
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1994.tb13100.x
更新日期：1994-06-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0701903
更新日期：1998-07-01 00:00:00
abstract：:1. It has been reported previously that the milrinone analogues, ethyl 5-cyano-1,6-dihydro-2-methyl-6-oxo-3 pyridine carboxylate (I) and ethyl 5-cyano-1,6-dihydro-2-ethyl-6-oxo-3 pyridine carboxylate (II) exert a positive inotropic effect (EC50 = 15.6 +/- 0.2 microM and 40.3 +/- 0.1 microM) both on spontaneously beati...
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pub_type： 杂志文章
doi：10.1111/j.1476-5381.1991.tb12519.x
更新日期：1991-12-01 00:00:00
abstract：:1. The convulsive effects of leptazol in the rat are potentiated by prior treatment with dexamphetamine.2. An intact dopamine synthesis is necessary for the potentiation of the convulsive action of leptazol.3. An intact noradrenaline synthesis is not necessary for this action of amphetamine, as long as the dopamine sy...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1969.tb09526.x
更新日期：1969-09-01 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.tb11109.x
更新日期：1985-12-01 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：1998-09-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0700913
更新日期：1997-02-01 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.13105
更新日期：2015-12-01 00:00:00
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journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705453
更新日期：2003-09-01 00:00:00
abstract：:1. The fall in arterial blood pressure with bradycardia that occurs on injection of clonidine into the cerebral ventricles and into the cisterna magna is attributed to an action on ;chemosensitive zones' situated at the ventral surface of the brain stem. This conclusion is based on the following results obtained in ca...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1111/j.1476-5381.1973.tb08532.x
更新日期：1973-12-01 00:00:00
abstract：:1. The functional changes in mesenteric arterioles of streptozotocin-induced diabetes were investigated by intravital microscopy. The mesentery was exteriorized from anesthetized rats, spread in a chamber, and superfused with Tyrode solution. All drugs tested were applied to the superfusing Tyrode solution. 2. Compare...
journal_title：British journal of pharmacology
pub_type： 杂志文章
doi：10.1038/sj.bjp.0705611
更新日期：2004-01-01 00:00:00
abstract：:The mechanism of the long duration of action of salmeterol at beta(2)-adrenoceptors has long been a matter of debate, and is still unresolved. Szczuka and colleagues have both summarized the position to date and suggested a new mechanistic contender, receptor rebinding. Despite this, they still do not come to any clea...
journal_title：British journal of pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1111/j.1476-5381.2009.00370.x
更新日期：2009-09-01 00:00:00
