Abstract：
:The human 5-HT transporter (hSERT) has two binding sites for 5-HT and 5-HT uptake inhibitors: the orthosteric high-affinity site and a low-affinity allosteric site. Activation of the allosteric site increases the dissociation half-life for some uptake inhibitors. The objectives of this study were 1) to identify hSERT mutations that inactivate the high-affinity site without affecting the allosteric site and 2) to observe allosteric effects in which hSERT binds R-citalopram with higher affinity than S-citalopram. Wild-type and mutant (Y95F, I172M, and Y95F/I172M) hSERTs were expressed in COS-7 cells, and their 5-HT uptake and uptake inhibitor-binding abilities were studied. The hSERT mutations did not alter affinities for 5-HT or paroxetine, but high-affinity binding of S-citalopram was severely affected, particularly by the I172M, and Y95F/I172M mutations - K(i) respectively 4 nM (wild-type), 35 nM, 1000 nM, and 17.100 nM (mutants). The allosteric site however, in wild-type hSERT and the three mutants was unaffected by the mutations as attenuation of the dissociation rate of the [(3)H]-paroxetine:hSERT complex in the presence of S-citalopram or paroxetine was the same for wild-type hSERT and the three mutants. Further, R-citalopram previously thought of as an inactive enantiomer strongly attenuated dissociation of the wild-type [(3)H]-imipramine:hSERT complex, whereas S-citalopram had almost no effect on this complex. These results suggest that 1: The allosteric site on hSERT is distinct from the site to which S-citalopram binds with high affinity. 2: The allosteric effects of R-citalopram on the dissociation of [(3)H]-imipramine from hSERT indicate that R-citalopram introduces a conformational change in hSERT.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Plenge P,Gether U,Rasmussen SGdoi
10.1016/j.ejphar.2007.03.055subject
Has Abstractpub_date
2007-07-12 00:00:00pages
1-9issue
1-2eissn
0014-2999issn
1879-0712pii
S0014-2999(07)00439-6journal_volume
567pub_type
杂志文章abstract：:We aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in common marmosets. The serum prolactin level gradually increased during the twice-daily administration of sulpiride and reached a plateau after 4 days. Sulpiride produced as big a response at 10 mg kg(-1) as at 50 mg kg(-1). In this...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00940-6
更新日期：1999-02-26 00:00:00
abstract：:In this study, we have examined the effect of acute and chronic administration of LY 277359, a putative 5-HT3 receptor antagonist, on the number of spontaneously active dopamine cells in the substantia nigra pars compacta (SNC or A9) and ventral tegmental area (VTA or A10). This was accomplished using the standard ext...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90163-k
更新日期：1991-12-17 00:00:00
abstract：:ATP, ADP, adenosine and AMP, but not adenine, inosine, or GMP, caused dose-related intestinal contractions when injected as intra-arterial bolus doses in vascularly perfused isolated segments of dog small bowel. The stimulatory effects of these agents were decreased by receptor densitization during exposure to high co...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(80)90203-4
更新日期：1980-07-11 00:00:00
abstract：:A microdialysis/smallbore chromatographic system was used to monitor changes in extracellular dopamine concentration in the striatum of the rat following administration of drugs that block catecholamine uptake. Analysis of 0.5 microliter of dialysate every 5 min showed dose-dependent elevations in extracellular dopami...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90592-9
更新日期：1987-07-23 00:00:00
abstract：:The impacts of prenatal propofol on cognition and emotion of offspring remain elusive. In the present study, pregnant rats in the second trimester were anesthetized with propofol. Neuronal apoptosis and proliferation was determined in fetuses and postnatal rats by detecting caspase-3 and BrdU expression. The offspring...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2018.11.032
更新日期：2019-01-15 00:00:00
abstract：:Some studies have suggested that drug tolerance observed following repeated benzodiazepine exposure may be associated with the development of a subsensitivity to gamma-aminobutyric acid (GABA) in dorsal raphe and hippocampal neurons. In other areas such as the substantia nigra such subsensitivity has not been found. T...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00053-2
更新日期：1996-04-22 00:00:00
abstract：:The existence of presynaptic autoreceptors modulating acetylcholine release from central cholinergic nerve endings was investigated by using rat hippocampal synaptosomes in a superfusion system. The presence of exogenous acetylcholine, carbachol or oxotremorine in the superfusion fluid produced a dose-dependent inhibi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90147-3
更新日期：1981-07-17 00:00:00
abstract：:Sex and stress hormones coordinate experience and behaviour with physiological regulations. In the brain the sex hormones act to promote the repertoire of affiliative and reproductive behaviours. Stress hormones target in particular brain circuits underlying emotional arousal and cognition. To exert these actions the ...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2009.10.017
更新日期：2010-01-10 00:00:00
abstract：:The purpose of this study was to investigate the antioxidant potential of umbelliferone, 7-hydroxy coumarin, and its role in the protection against radiation-induced oxidative damage in cultured human blood lymphocytes. It was found that the antioxidant effect of umbelliferone was dose dependent in hydroxyl (OH(•)), s...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.09.003
更新日期：2011-12-15 00:00:00
abstract：:Ifoxetine (CGP 15210 G; (+/-)-bis-[cis-3-hydroxy-4-(2,3-dimethyl-phenoxy)]-piperidine sulfate) prevented the depletion of serotonin (5-HT) induced by H 75/12 and p-chloromethamphetamine in the rat brain, and that caused by endogenously released dopamine after the combined administration of haloperidol and amfonelic ac...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90177-9
更新日期：1986-10-14 00:00:00
abstract：:Intracellular Ca2+ overload induced by hypoxia-reoxygenation alters Ca2+ homeostasis, which plays an important role in myocardial cell injury. Even though propofol is known as a radical scavenger with Ca2+ channel blocking properties, little is known about cardioprotective effect associated with Ca2+ homeostasis in ca...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.07.027
更新日期：2008-10-10 00:00:00
abstract：:The effect of DL-propranolol on NO release in perfused rat hindquarters was studied by using oxyhemoglobin as a capture system to allow the quantitative assay of NO production. In some experiments the stable prostacyclin metabolite 6-keto-PGF1 alpha (6-keto) was simultaneously assayed. We observed that: (1) DL-propran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90686-x
更新日期：1992-03-24 00:00:00
abstract：:We examined whether danazol has a direct action on ovarian steroid secretion and/or uterine prostaglandin (PG) F2 alpha catabolic activity in immature rats in which the first ovulation was induced and in adult ovariectomized rats. The preovulatory surge of estradiol and progesterone was markedly suppressed together wi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90264-5
更新日期：1992-01-28 00:00:00
abstract：:In the rat distal colon, 5-hydroxytryptamine (5-HT)-induced Cl- secretion is seen as a rise in short circuit current (Isc). We investigated the 5-HT receptor mediating 5-HT-induced Cl- secretion in the rat distal colon. Rat distal colon was prepared either by stripping away the muscularis propria with the neural gangl...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00752-0
更新日期：1996-03-07 00:00:00
abstract：:The aim of the present investigation was to assess neuroprotection exerted by diazepam (0.1-25 microM) in rat cortical brain slices subjected to oxygen-glucose deprivation and reoxygenation. Neuronal injury and neuroprotection were assessed by measuring the release of glutamate and lactate dehydrogenase and tissue wat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2006.12.030
更新日期：2007-04-30 00:00:00
abstract：:The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depresse...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(93)90690-j
更新日期：1993-01-26 00:00:00
abstract：:The function of gamma-aminobutyric acid type A receptors (GABA(A) receptors) is enhanced by various clinically important drugs including benzodiazepines that act on an allosteric site formed at the interface between the alpha and gamma subunits. In contrast to classical benzodiazepines, the novel pyrazolopyrimidine in...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2007.10.016
更新日期：2008-02-02 00:00:00
abstract：:We investigated the effects of antithrombin, a plasma inhibitor of coagulation factors, in rats with puromycin aminonucleoside-induced nephrosis, which is an experimental model of human nephrotic syndrome. Antithrombin (50 or 500 IU/kg/i.v.) was administered to rats once a day for 10 days immediately after the injecti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.04.065
更新日期：2008-07-28 00:00:00
abstract：:The antagonistic effects of a new inositol phosphate derivative, D-myoinositol-1,2,6-trisphosphate (PP56), on pressor responses to preganglionic sympathetic nerve stimulation and exogenously administered phenylephrine or neuropeptide Y (NPY) were investigated in vivo in the pithed rat. In this model an intravenous (i....
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(91)90853-i
更新日期：1991-11-12 00:00:00
abstract：:The development of anticonvulsant tolerance with RO 16-6028, a benzodiazepine receptor partial agonist, was assessed in mice using an i.v. infusion of pentylenetetrazol as the convulsive stimulus. In contrast to other benzodiazepines tested previously in this seizure model the anticonvulsant protection afforded by RO ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90788-1
更新日期：1988-03-01 00:00:00
abstract：:Chlorin derivatives have been known for their biological activities. Especially due to their advanced electron transfer capacity they have been used as photodynamic therapy agent both at clinical and laboratory scales. Photodynamic therapy (PDT) against cancer or an infectious disease aims the development of less side...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172980
更新日期：2020-04-15 00:00:00
abstract：:The purposes of the present study were to clarify whether some Cl(-) channels exist in rat pleural mesothelial cells, and to investigate functional and molecular characteristics of these channels. Electrophysiological recordings were performed at room temperature using the whole-cell configuration of the patch-clamp t...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2009.05.001
更新日期：2009-07-01 00:00:00
abstract：:The pruritogenic potency of tryptase and its involvement in anti-pruritic effect of intravenous nafamostat mesilate (NFM) were studied in mice. An intradermal injection of tryptase (0.05-1 ng/site) elicited scratching in ICR mice, while chymase was without effects at doses of 0.05-50 ng/site. The dose-response curve o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.11.021
更新日期：2006-01-13 00:00:00
abstract：:SL 84.0418 (2-(4,5-dihydro-1H-imidazol-2-yl)-1,2,4,5-tetrahydro-2-propyl-pyrrolo[3, 2,1- hi]-indole hydrocholoride) is a novel alpha 2-adrenoceptor antagonist which possesses anti-hyperglycaemic properties in vitro study, we tested its effects on insulin release from isolated mouse islets. In the presence of 15 mM glu...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90366-2
更新日期：1994-03-11 00:00:00
abstract：:Our data indicate that estrogens and progesterone can regulate the number of GABA receptors (as detected by [3H]muscimol binding assay) in rat brain. Both hormones act in selected areas. The extent of the effect (up to 160% increase) and the number of areas responsive suggest that sex hormones may play a very importan...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(84)90205-x
更新日期：1984-08-03 00:00:00
abstract：:The effect of Bay K 8644 on contractile responses to angiotensin II (AII) was investigated in rabbit aorta. Bay K 8644 alone did not elicit contraction while contractile responses to AII were enhanced at low concentrations (10(-8), 3 X 10(-8), 10(-7) M) and depressed at a higher concentration (10(-6) M). The potentiat...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90755-7
更新日期：1986-07-15 00:00:00
abstract：:The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes were inserted into the subcutaneous tissue of the plantar surface of rat hind paws. Samples wer...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(00)00742-1
更新日期：2000-11-17 00:00:00
abstract：:Rhein is one of the anthraquinones components of Rheum. It shows excellent clinical efficacy and is widely used in the management of several disease conditions including tumors, inflammation, diabetic nephropathy, and viral infections. In this review, we summarize the recent studies on the pharmacological activities o...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2021.173908
更新日期：2021-01-27 00:00:00
abstract：:N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide, maleate (ABT-866) is a novel alpha(1)-adrenoceptor agent with mixed pharmacological properties in vitro. Compared to phenylephrine, ABT-866 demonstrates intrinsic activity at the alpha(1A)-adrenoceptor subtype present in the rabbit urethra (pD(2) = 6.22, with 80% ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(02)01976-3
更新日期：2002-08-02 00:00:00
abstract：:FR134043, disodium(Z,1S,15S,8S,24S,27R,29S,34S,37R)-29-ben zyl-21-ethylidene-27-hydroxy-15-isobutyrylamino-34-isopropyl-31,37 -dimethyl-10,16,19,22,30,32,35,38-octaoxo-36-oxa-9,11,17,20,23,28, 31,33-octaazatetracyclo[16.13.6.1(24),(28).0(3),(8)]octatricont a-3,5,7-trien-5,6-diyl disulfate, is a water-soluble inhibitor...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(98)00028-4
更新日期：1998-03-26 00:00:00
