Abstract:
:Since the melanocortin MC3 and melanocortin MC4 receptors are the main melanocortin receptor subtypes expressed in rat brain, we characterized the activity and affinity of nine melanocortin receptor ligands using these receptors in vitro, as well as their activity in a well-defined melanocortin-induced behavior in the rat: grooming behavior. We report here that [D-Tyr4]melanotan-II and RMI-2001 (Ac-cyclo-[Cys4, Gly5, D-Phe7, Cys10]alpha-MSH-NH2) have significantly higher affinity and potency on the rat melanocortin MC4 receptor as compared to the rat melanocortin MC3 receptor. Nle-gamma-MSH (melanocyte-stimulating hormone) was the only ligand with higher affinity and potency on the rat melanocortin MC3 receptor. The potency order of melanocortin MC4 receptor agonists, but not that of melanocortin MC3 receptor agonists, fitted with the potency of these ligands to stimulate grooming behavior, when administered intracerebroventricularly. SHU9119 (Ac-cyclo-[Nle4, Asp5, D-Nal(2)7, Lys10]alpha-MSH-(4-10)-NH2) and RMI-2005 (Ac-cyclo-[Cys4, Gly5, D-Na](2)7, Nal(2)9, Cys10]alpha-MSH-(4-10)-NH2) were able to inhibit alpha-MSH-induced melanocortin receptor activity in vitro, as well as alpha-MSH-induced grooming behavior. Melanotan-II, [Nle4-D-Phe7]alpha-MSH and RMI-2001 were also effective in inducing grooming behavior when administered intravenously. In the absence of purely selective melanocortin MC(3/4) receptor ligands, we demonstrated that careful comparison of ligand potencies in vitro with ligand potencies in vivo, could identify which melanocortin receptor subtype mediated alpha-MSH-induced grooming behavior. Furthermore, blockade of novelty-induced grooming behavior by SHU9119 demonstrated that this physiological stress response is mediated via activation of the melanocortin system.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Adan RA,Szklarczyk AW,Oosterom J,Brakkee JH,Nijenhuis WA,Schaaper WM,Meloen RH,Gispen WHdoi
10.1016/s0014-2999(99)00465-3keywords:
subject
Has Abstractpub_date
1999-08-13 00:00:00pages
249-58issue
3eissn
0014-2999issn
1879-0712pii
S0014-2999(99)00465-3journal_volume
378pub_type
杂志文章abstract::A cDNA clone coding for the guinea pig leukotriene B4 (BLT) receptor has been isolated from a lung cDNA library. The guinea pig BLT receptor has an open reading frame corresponding to 348 amino acids and shares 73% and 70% identity with human and mouse BLT receptors, respectively. Scatchard analysis of membranes prepa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00514-2
更新日期:1999-09-10 00:00:00
abstract::An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)90811-7
更新日期:1994-12-27 00:00:00
abstract::To investigate the putative rewarding effects of atomoxetine, a non-stimulant medication for Attention-deficit/hyperactivity disorder (ADHD), we conducted conditioned place preference (CPP) tests in an animal model of ADHD, the spontaneously hypertensive rat (SHR). The effects of drug pre-exposure were also evaluated,...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.05.057
更新日期:2011-09-30 00:00:00
abstract::Delta9-tetrahydrocannabinol induces [Ca2+]i increases in DDT1MF-2 smooth muscle cells. Both Ca2+ entry and release from intracellular Ca2+ stores were concentration dependently activated. The Ca2+ entry component contributed most to the increases in [Ca2+]i. Stimulation with delta9-tetrahydrocannabinol after functiona...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)01254-5
更新日期:1997-10-01 00:00:00
abstract::The administration of the synthetic and stable opioid peptide[D-Ala2,MePhe4,Met(O)5o1]enkephalin (FK 33-824) at the dose of 0.2 mg/kg i.v. induced a rise in plasma levels of prolactin in the rat, an effect which was prevented by 1 mg/kg i.v. of the opiate antagonist naloxone. A simultaneous i.v. injection of 20 microg...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(82)90009-7
更新日期:1982-01-22 00:00:00
abstract::Lergotrile and apomorphine, two direct-acting dopamine agonists, caused marked hyperglycemia in fasted rats, while compounds which release endogenous dopamine (amphetamine, methylphenidate) or inhibit dopamine reuptake (LR5182), failed to elevate blood glucose. The effect of lergotrile was dose dependent, causing bloo...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(79)90028-1
更新日期:1979-10-26 00:00:00
abstract::Growing evidence recommends incorporating the concept of drug-target residence times within drug development and screening programs. For many targets, systematic research for binding kinetics is emerging and reported, as in case of the histamine H3 receptor. Alternatively, fluorescent methods based on Foerster resonan...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.01.041
更新日期:2019-04-05 00:00:00
abstract::Oral methylnalorphine ( methylnalorphinium ) caused a dose-dependent selective inhibition of inflammatory hyperalgesia (measured in the rat by a modified version of the Randall- Selitto test) without affecting the oedema. When subcutaneously injected, repeated doses of morphine for 5 days caused progressive analgesic ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90428-x
更新日期:1984-03-16 00:00:00
abstract::Lung cancer is a disease with increasing morbidity worldwide in recent years. Approaches such as chemotherapy and biological targeting for its treatment are urgently needed. Epithelial-mesenchymal transition (EMT) is an important initiation stage for tumor cells to acquire invasive and metastatic abilities. Increasing...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2019.172630
更新日期:2019-11-05 00:00:00
abstract::The intracerebral injection technique was used to apply dopamine directly into dopamine-containing areas of the mesolimbic system, the nucleus accumbens septi, tuberculum olfactorium and nucleus amygdaloideus centralis. 200 mug dopamine injected bilaterally into the nucleus accumbens septi caused a stereotyped sniffin...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(75)90326-x
更新日期:1975-05-01 00:00:00
abstract::Endotoxin (Escherichia coli lipopolysaccharide 0111:B4, 3 mg/kg i.v.) induced the expression of a calcium-independent nitric oxide (NO) synthase, determined after 5 h in cardiac, hepatic, pulmonary and renal tissues, as assessed by the conversion of radiolabelled L-arginine to L-citrulline. This widespread induction o...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00281-o
更新日期:1995-09-05 00:00:00
abstract::The thromboxane mimetic U46619 (11 alpha,9 alpha-epoxymethano PGH2) increased 45Ca2+ uptake in sheep coronary artery rings. A larger increase occurred in endothelium-denuded than in endothelium-inact rings (increase in 45Ca2+ uptake: endothelium intact = 9.6 +/- 3.8, endothelium-denuded = 33.2 +/- 8.1 nmol g-1), in ag...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0926-6917(94)90007-8
更新日期:1994-08-03 00:00:00
abstract::A C-fibre reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anaesthetised rats. Such reflex responses can be inhibited by applying noxious conditioning stimuli to heterotopic areas of the body. These inhibitory processes have be...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00600-1
更新日期:1995-12-29 00:00:00
abstract::The aim of the present study was to examine the influence of ifenprodil (a non-competitive NMDA receptor antagonist which also blocks 5-HT3 receptors and alpha1-adrenoceptors) on the effects of ethanol in the mouse in vivo and to elucidate the role of various receptors in these actions. The ethanol (4 g/kg i.p.)-induc...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00393-3
更新日期:1999-07-14 00:00:00
abstract::This study examined the potential of the selective extra-synaptic α5-GABAA receptor inhibitor S44819 (Egis-13529) to improve cognitive performance in preclinical models of vascular cognitive impairment (VCI). Chronic hypoperfusion of the brain in mice was induced by permanent occlusion of the right common carotid arte...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2018.07.015
更新日期:2018-09-05 00:00:00
abstract::The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.03.002
更新日期:2005-08-22 00:00:00
abstract::[3H]Prostaglandin E2 (PGE2) binding sites were 10-fold enriched from a porcine fundic mucosal homogenate by differential centrifugation and subsequent discontinuous sucrose gradient separation. PGE2 bound with an activation energy of 66 kJ/mol to a single class of sites with an affinity of 1.5 +/- 0.4 nM and a capacit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90780-7
更新日期:1988-03-01 00:00:00
abstract::Inflammation, closely associated with obesity, is emerging as an important risk factor for the pathophysiological development of atherosclerosis and diabetes mellitus. Fat balance is critical in the aetiology of obesity. Lipoprotein lipase is an important enzyme in lipid metabolism. The aim of this study was to invest...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.04.032
更新日期:2006-07-01 00:00:00
abstract::Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (dbcAMP) at varying concentrations as low as 1 X 10(-4)M. A positive inotropic effect was observed with all concentrations of dbcAMP. Concomitant administration of 5 X 10(-4)M monobutyryl guanosine 3',5'-monophosphat...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(76)90280-6
更新日期:1976-03-01 00:00:00
abstract::Mouse gastric fundus strips were relaxed by ultraviolet light (UV) irradiation, exogenous nitric oxide (NO), isoproterenol, S-nitrosoglutathione, S-nitroso-L-cysteine and S-nitroso-N-acetyl-penicillamine. Glutathione did not affect relaxations in response to UV irradiation, exogenous NO and isoproterenol while inhibit...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)02098-8
更新日期:2002-08-30 00:00:00
abstract::Substance P causes histamine release from rat peritoneal mast cells probably through direct activation of a specific G protein at micromolar concentrations. We found that peritoneal mast cells of a substrain of Wistar rats (Std:Wistar) responds to nanomolar concentrations of substance P by releasing histamine in a con...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(99)00338-6
更新日期:1999-06-18 00:00:00
abstract::We show that cisplatin resistance in certain lung cancer cell lines can be reversed through inhibition of mTOR (mammalian Target of Rapamycin). These cell lines appear to possess high levels of phospho-mTOR, phospho-AKT and other growth-related proteins, such as hTERT (human telomerase reverse transcriptase), and Cycl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.06.028
更新日期:2008-09-04 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::Fibroblast growth factor 21 (FGF21) has been identified as a potent and robust metabolic regulator. Administration of recombinant FGF21 protein to rodents and rhesus monkeys exerts strong anti-diabetic effects. Previous studies have demonstrated that FGF21 inhibits glucose output in the rat H4IIE hepatoma cell line. W...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2012.11.065
更新日期:2013-02-28 00:00:00
abstract::The present study was to investigate the neuroprotective efficacy and mechanism of Forsythoside B. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 1 h followed by reperfusion for 23 h. Rats received an intravenous bolus injection of Forsythoside B at 15 min after reperfusion. The result...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.04.055
更新日期:2010-08-25 00:00:00
abstract::The anticonvulsant activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline (MeTHIQ--an endogenous parkinsonism-preventing substance) administered alone and in combination with four conventional antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and valproate) was determined in the mouse maximal electroshock-indu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2008.11.049
更新日期:2009-01-14 00:00:00
abstract::Homovanillic acid (HVA) was measured in rat caudate and pre-frontal cortex 3 h following a single dose of a variety of neuroleptics. Thioridazine, haloperidol, fluphenazine, and metoclopramide increased HVA levels in caudate more than in pre-frontal cortex; whereas sulpiride and clozapine produced greater increases in...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(84)90438-2
更新日期:1984-03-16 00:00:00
abstract::We have examined the motor responses to the dopamine D(3) receptor-preferring agonist, S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-1-benzopyranol[4,3-b]-1,4-oxazin+ ++-9-ol ((+)-PD128,907), by non-habituated male rats during postnatal development. (+)-PD128,907 (0.025 and 0.1 mg/kg) increased motor activity ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00112-6
更新日期:2000-03-24 00:00:00
abstract::Bacterial lipopolysaccharide and other immunostimulants induce gene expression of an isoform of nitric oxide synthase (iNOS) in vascular smooth muscle cells. This process is dependent on nuclear factor-kappa B (NF-kappa B) activation. The aim of this study was to investigate whether the NF-kappa B and Akt signaling pa...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.09.034
更新日期:2003-11-28 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