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 in the rat cerebral cortex and human ORL1 receptors expressed in HEK293 cells with K(i) values of 0.76 and 0.50 nM, respectively. W-212393 concentration-dependently stimulated GTPgamma(35)S binding and its efficacy was similar to nociceptin/orphanin FQ (N/OFQ), suggesting that W-212393 is a full agonist at ORL1 receptors. W-212393 dose-dependently occupied ORL1 receptors following intraventricular or intraperitoneal administration, suggesting that W-212393 is a brain-penetrating compound. W-212393 (100 nM) and N/OFQ (100 nM) significantly suppressed the activity of spontaneously firing rat suprachiasmatic nucleus neurons. These suppressive effects were blocked by an ORL1 receptor antagonist, J-113397 (1 microM). W-212393 (3 mg kg(-1), i.p.) induced a significant phase advance at circadian time 6 (CT6) and CT9, but not at other CTs. The magnitude of the W-212393 (0.3-3 mg kg(-1), i.p.)-induced phase advance was dose-dependent and greater than those produced by 8-hydroxy-2-(di-n-propylamino)tetralin (0.3-3 mg kg(-1), i.p.) or melatonin (0.3-3 mg kg(-1), i.p.). The W-212393 (3 mg kg(-1), i.p.)-induced phase advance was antagonized by J-113397 (10 mg kg(-1), i.p.).W-212393 (3 mg kg(-1), i.p.) significantly accelerated the re-entrainment of the body temperature rhythm to a 6 h advanced light-dark cycle. These results indicate that activation of ORL1 receptors contributes to the circadian entrainment and W-212393 may represent an interesting agent for the study of circadian rhythms.
journal_name
Br J Pharmacoljournal_title
British journal of pharmacologyauthors
Teshima K,Minoguchi M,Tounai S,Ashimori A,Eguchi J,Allen CN,Shibata Sdoi
10.1038/sj.bjp.0706311subject
Has Abstractpub_date
2005-09-01 00:00:00pages
33-40issue
1eissn
0007-1188issn
1476-5381pii
0706311journal_volume
146pub_type
杂志文章abstract:LINKED ARTICLES:This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc. ...
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abstract::The electrically-evoked contractions of the rat vas deferens were selectively inhibited by beta-endorphin, the preparation being much less sensitive to enkephalins and narcotic analgesic drugs. However, introduction of D-Ala in position 2 of [Leu]-enkephalin enhanced the activity of the opioid peptide to the order of ...
journal_title:British journal of pharmacology
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abstract::1,1-Azobis[3-methyl-2-phenylbenzimidazolinium]dimethanesulphonate (AH 10407) has an ultrashort, competitive neuromuscular blocking action in the mouse, cat, dog, Cynamolgus monkey and cotton-eared marmoset. 2 AH 10407 is chemically unstable in bicarbonate-containing solutions and is degraded to inactive products. The ...
journal_title:British journal of pharmacology
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abstract::1. Acute moderate hypoxia modifies the catalytic activity and expression of certain isoenzymes of hepatic cytochrome P450 (P450). The aim of this study was to document whether hypoxia affects hepatic P450 directly or through the release of serum mediators. 2. Rabbits were subjected to a FiO(2) of 8% for 48 h, sacrific...
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abstract::Leukotriene B4 (LTB4) is a potent leukocyte chemoattractant, acting on specific receptors, BLT receptors. The aim of this study was to examine the mechanism of action of LTB4 in the guinea-pig lung, using strips of lung parenchyma (GPLP), spirals of trachea (GPT) and bronchus (GPB) and rings of pulmonary artery (GPPA)...
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abstract::Hydrogen sulfide (H(2)S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H(2)S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide ...
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abstract::1. The effects of chronic dietary supplementation with omega 3 polyunsaturated fatty acids on endothelium-dependent relaxations were examined in isolated coronary microvessels of the pig. 2. Animals were maintained for four weeks with or without dietary supplementation of purified eicosapentaenoic acid (3.5 g daily) a...
journal_title:British journal of pharmacology
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abstract::5-Hydroxytryptamine(1B/1D) (5-HT(1B/1D)) receptor coupling to contraction was investigated in endothelium-denuded rabbit isolated renal arteries, by simultaneously measuring tension and intracellular [Ca(2+)], and tension in permeabilized smooth muscle cells. In intact arterial segments, 1 nM - 10 microM 5-HT failed t...
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doi:10.1111/j.1476-5381.1981.tb16764.x
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abstract:BACKGROUND AND PURPOSE:Retinoids, through their activation of retinoic acid receptors (RARs) and retinoid X receptors, regulate diverse cellular processes, and pharmacological intervention in their actions has been successful in the treatment of skin disorders and cancers. Despite the many beneficial effects, administr...
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abstract::The last five years have witnessed a remarkable resurgence of interest in myocardial reperfusion injury. Reperfusion is absolutely essential to salvage ischaemic myocardium but experimental and clinical studies show that reperfusion-associated injury may mask the full benefits of prompt reperfusion in acute myocardial...
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abstract::1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists ...
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abstract::Annexin A2 (AnxA2) was originally identified as a substrate of the pp60v-src oncoprotein in transformed chicken embryonic fibroblasts. It is an abundant protein that associates with biological membranes as well as the actin cytoskeleton, and has been implicated in intracellular vesicle fusion, the organization of memb...
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