Abstract：
:The recent elucidation of the primary structures of different melatonin receptors as well as the deduction of the secondary structure of rhodopsin has allowed us to construct a model for melatonin recognition at its G protein-coupled receptor. To achieve this, we have used the quantum mechanics method Austin model 1 to fully optimize the structures of melatonin and several analogs. We also synthesized three compounds and used the three-dimensional analysis comparative molecular field analysis (CoMFA) to generate a model for the structure-activity relationships of melatonin and 27 melatonin-like compounds. This model predicted with good accuracy the affinities of the synthesized compounds for the melatonin receptor. We propose that recognition of the functional moieties of melatonin occurs through specific interaction of these moieties with fully conserved amino acid residues present in transmembrane helices V, VI and VII of the melatonin receptor. These residues are not found in other members of the G protein-coupled receptor family. The rhodopsin-based model can explain the importance of some structural features of melatonin and related active compounds.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Navajas C,Kokkola T,Poso A,Honka N,Gynther J,Laitinen JTdoi
10.1016/0014-2999(96)00114-8subject
Has Abstractpub_date
1996-05-23 00:00:00pages
173-83issue
1-3eissn
0014-2999issn
1879-0712pii
0014-2999(96)00114-8journal_volume
304pub_type
杂志文章abstract：:A new analogue of ANF (atrial natriuretic factor), NNC 70-0270, was tested in various isolated artery preparations. In the rabbit aorta and renal artery NNC 70-0270 was compared with atriopeptin III and the relative inhibitory potency against noradrenaline-induced contractions (atriopeptin III = 1) was found to be 5 a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90764-h
更新日期：1991-11-19 00:00:00
abstract：:The purpose of this study was to examine the influence of ageing on the alterations in binding characteristics of adrenoceptors and membrane phospholipid fatty acids in rat heart following repeated administration of epinephrine. The maximal number of binding sites (Bmax) and dissociation constant (Kd) of [3H]prazosin ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(95)90150-7
更新日期：1995-05-26 00:00:00
abstract：:The contractile response of vascular smooth muscle is known to consist of fast and slow components of contraction. We investigated the effect of norepinephrine and angiotensin-II on these functional properties of vascular smooth muscle in a quantitative fashion by analyzing the velocity of isometric tension developmen...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90274-5
更新日期：1980-03-21 00:00:00
abstract：:Inhibition of interleukin-6 (IL-6) holds significant promise as a therapeutic approach for triple negative breast cancer (TNBC). We previously reported that phenylmethimazole (C10) reduces IL-6 expression in several cancer cell lines. We have identified a more potent derivative of C10 termed COB-141. In the present wo...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2017.03.049
更新日期：2017-05-15 00:00:00
abstract：:Thiazolidinedione and isoxazolidinedione insulin sensitizers activate peroxisome proliferator-activated receptor gamma (PPAR gamma). Some thiazolidinediones modify ion channels in smooth muscles; however, the mechanism by which their actions occur has not been clarified. We, thus, examined the effects of three thiazol...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01047-0
更新日期：2001-06-29 00:00:00
abstract：:Here we provide the first pharmacological exploration of the impact of acute central nervous system exposure to three recently developed ghrelin receptor (GHS-R1A) ligands on food intake and on the electrical activity of the target cells for ghrelin in the hypothalamus. Central (i.c.v) injection of GHS-R1A antagonists...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.03.066
更新日期：2009-06-10 00:00:00
abstract：:Striatal neurons in primary culture express a wide variety of adenylate cyclase-coupled receptors, and particularly dopamine (DA) D1 receptors, which are known to induce an increase in cyclic AMP production. To study desensitization of those receptor-mediated responses, neurons were incubated in the presence of satura...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(90)90121-d
更新日期：1990-10-30 00:00:00
abstract：:The spasmogenic activity of caffeine (10 mM) was evaluated in tracheal strips obtained from control and sensitized guinea-pigs then pretreated with indomethacin (2.8 microM) and cooled to 20 degrees C. The contraction elicited by caffeine was inhibited by verapamil (100 microM), trifluoperazine (100 and 500 microM) an...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90073-8
更新日期：1988-12-13 00:00:00
abstract：:H89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) is a compound characterized in vitro as a potent and selective inhibitor of protein kinase A (PKA). In this study, we found that H89 reduced the phosphorylation of the myosin regulatory light chain (MRLC) at Thr-18/Ser-19 and induced disassembly of stre...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.05.029
更新日期：2008-08-20 00:00:00
abstract：:The effects of angiotensin I-converting enzyme (ACE) inhibitors and bradykinin (BK) on prostacyclin (PGI2) production in isolated arterial tissue were investigated. Rings of rat abdominal aorta were incubated in Krebs-Ringer bicarbonate buffer and PGI2 generation was assessed by the determination of its stable hydroly...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(90)94795-y
更新日期：1990-03-13 00:00:00
abstract：:(+/-)-SDZ NVI 085 (3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9- methylthio-2H-naphth [2,3-b]-1,4-oxazine hydrochloride), an alpha 1-adrenoceptor agonist, produced a concentration-dependent relaxation (pIC50 of 7.2 +/- 0.1) in the isolated caudal artery of rat precontracted with serotonin (5-hydroxytryptamine, 5-HT,...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00850-0
更新日期：1996-02-15 00:00:00
abstract：:The purpose of the present study was to test whether kava extract and its constituents kawain, dihydrokawain, methysticin, dihydromethysticin and yangonin provide protection against ischemic brain damage. To this end, we used a model of focal cerebral ischemia in mice and rats. Ischemia was induced by microbipolar coa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90037-5
更新日期：1992-05-14 00:00:00
abstract：:Persistent hyperglycemia increases a systemic oxidative stress, causing the onset of vascular endothelial dysfunction and atherosclerosis. Diallyl trisulfide (DAT), a natural organosulfur compound in garlic, has been reported to have actions of dilating blood vessels and antibacteria, etc. In this study, models of obe...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2014.01.010
更新日期：2014-02-15 00:00:00
abstract：:Previous work from our laboratory has indicated that ovine prolactin can produce a rapid stimulation (within 1 h) of dopamine release from nigrostriatal and mesolimbic dopaminergic neurons of male rats. In the present experiment we attempted to determine whether this effect of prolactin was a function of an increase i...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(89)90361-0
更新日期：1989-08-03 00:00:00
abstract：:We have recently proposed that retinoic acid receptor (NR1B) is a promising target of neuroprotective therapy for intracerebral hemorrhage, since pretreatment of mice with an NR1B1/NR1B2 agonist Am80 attenuated various pathological and neurological abnormalities associated with the disease. In the present study we fur...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2012.03.023
更新日期：2012-05-15 00:00:00
abstract：:Adjuvant arthritis in rats was induced by a single subcutaneous injection of Freund adjuvant into a hind paw. The injected paws' mean volume increased continuously by 80 +/- 26% after 6 h (acute local response). The injected paw displayed a biphasic response peaking at day 1-2 decreasing to day 5, then increased to da...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(82)90234-5
更新日期：1982-02-26 00:00:00
abstract：:PPARα belongs to the peroxisome-proliferator-activated receptors (PPARs) family that consists of PPARα, PPARδ, and PAPRγ. Activation of PPARα by ligands including fatty acids and their derivatives as well as some synthetic compounds regulates tumor progression in various tissues. Activated PPARα inhibits or promotes t...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2015.09.027
更新日期：2015-10-15 00:00:00
abstract：:Statin medications diminish cholesterol biosynthesis and are commonly prescribed to reduce cardiovascular disease. Statins also reduce production of ubiquinol, a vital component of mitochondrial energy production; ubiquinol reduction may contribute to rhabdomyolysis. Human rhabdomyosarcoma cells were treated with eith...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.04.009
更新日期：2013-07-05 00:00:00
abstract：:Prostaglandin E2 (PGE2) is a prostanoid with diverse actions in health and disease. In chronic respiratory diseases driven by inflammation, PGE2 has both positive and negative effects. An enhanced understanding of the receptor-mediated cellular signalling pathways induced by PGE2 may help us separate the beneficial pr...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2016.04.041
更新日期：2016-07-05 00:00:00
abstract：:The effects of a highly selective kappa antagonist, nor-binaltorphimine (nor-BNI), on the development of tolerance to morphine analgesia and physical dependence on morphine were examined. Pretreatment with nor-BNI (5 mg/kg s.c.) 2 h prior to injection of morphine or a selective kappa agonist, U-50,488H, significantly ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90237-x
更新日期：1992-03-17 00:00:00
abstract：:Bimoclomol is a new compound that improves cell survival under experimental stress conditions partly by increasing intracellular heat shock proteins (HSPs). HSPs, especially HSP70, play a cytoprotective role in the rat heart. Rat neonatal cardiomyocytes were used to determine the ability of bimoclomol to induce HSP70 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01551-5
更新日期：2002-01-18 00:00:00
abstract：:The cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) has a higher affinity for the dopamine transporter and may be potentially useful in interfering with cocaine's actions in brain. However, imaging studies have demonstrated displacement of tracer doses of [123I]RTI-...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00698-2
更新日期：1996-01-25 00:00:00
abstract：:In the Brattleboro rat with diabetes insipidus vasopressin V2 receptor mRNA and the mRNA of various adenylyl cyclase (AC) isoforms are moderately reduced compared with those of normal rats. In the present study renal vasopressin V2 receptor mRNA was modestly higher (by 34%), as was expression of AC 5, 6 and 9 mRNAs (u...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01461-1
更新日期：1998-01-02 00:00:00
abstract：:5-methoxy-N,N-dimethyltryptamine (5-MeODMT) produced a dose-dependent decrease in the discharge rate of serotonin-containing neurons in the dorsal raphe nucleus of freely moving cats. This ranged from a 15% decrease at 10 microgran/kg, i.m., to a virtual complete depression of activity at 250 microgram/kg. 5-MeODMT's ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(79)90406-0
更新日期：1979-02-15 00:00:00
abstract：:Carbamazepine, a drug effective in pain, seizure, and affective disorders, was screened for its ability to interact with a variety of neurotransmitter and neuromodulator binding sites on brain membranes. The most potent effect was observed on adenosine antagonist ( [3H]DPX) binding to the adenosine receptor (KI = 3.5 ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90135-8
更新日期：1983-09-30 00:00:00
abstract：:In the isolated perfused guinea-pig heart low-pH buffer (pH 5), lactic acid (5 mM), capsaicin (10(-7) M) and nicotine (10(-4) M) all evoked a clear-cut release of calcitonin gene-related peptide (CGRP) from sensory nerves. Incubation with the proposed capsaicin receptor antagonist, capsazepine (10(-5) M), significantl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90792-3
更新日期：1992-10-06 00:00:00
abstract：:We designed a randomized controlled study to identify and compare the liver tissue responses in systemic hypoxia and resuscitation with 21% and 100% oxygen using an animal model of neonatal hypoxia and reoxygenation. Twenty-seven piglets (1-3 days old, weight 1.5-2.0 kg) were acutely instrumented and mechanically vent...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.11.019
更新日期：2008-02-12 00:00:00
abstract：:The anti-migraine drug, eletriptan [(R)-3-(1-methyl-2-pyrrolidinylmethyl)-5-[2-(phenylsulphonyl )ethyl]-1 H-indole; UK-116,044], is a novel 5-HT(1B/1D) receptor agonist. In this paper, the regional vasoconstrictor profile of eletriptan, in comparison with sumatriptan, was examined in the anaesthetised dog. The inhibit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00240-5
更新日期：2000-06-09 00:00:00
abstract：:The effect of some tryptaminergic drugs on electroshock fighting behaviour in rats was determined. Reserpine and tetrabenazine reduced the fighting responses while 5-hydroxytryptophan increased the fighting responses in normal as well as reserpine-treated animals. p-Chlorophenylalanine, a specific depletor of brain se...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90149-7
更新日期：1976-10-01 00:00:00
abstract：:Detailed antagonist competition curves for [3H]prazosin-labelled binding sites in rat cerebral cortex membranes reveal anomalous binding characteristics. Dihydroergocryptine and indoramine compete in a steep, monophasic manner while WB4101 and phentolamine exhibit shallow competition curves. Computer-assisted analysis...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90432-7
更新日期：1985-02-26 00:00:00
