Abstract：
:Based on the ability of many receptors to amplify NIH 3T3 cells, we developed a high throughput assay of cloned receptor pharmacology. In this assay, receptors are transiently co-expressed with the marker enzyme beta-galactosidase. Receptors that induce cellular proliferation select and amplify the cells that also express the marker, thus the ability of ligands to alter receptor activity are reported as changes in enzyme activity. We used this assay to evaluate the pharmacology of agonist and antagonist ligands for five cloned human muscarinic receptor subtypes (m1-m5). When cells were transfected with subtypes that prefer the G-protein Gq (m1, m3, m5) robust increases in enzyme activity were observed. The subtypes that prefer Gi (m2 and m4) only induced beta-galactosidase when co-expressed with a chimera between the G-proteins Gq and Gi (Gq-i5). Overall, the rank-order of potency and intrinsic activity of most of the tested ligands were in remarkably good agreement with earlier results using cloned cell lines and isolated tissues. These data demonstrate that a high throughput colorimetric assay performed in 96-well plates can be used to evaluate subtle differences the pharmacology of ligands for cloned muscarinic receptor subtypes.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Bräuner-Osborne H,Brann MRdoi
10.1016/0014-2999(95)00639-7subject
Has Abstractpub_date
1996-01-04 00:00:00pages
93-102issue
1eissn
0014-2999issn
1879-0712pii
0014299995006397journal_volume
295pub_type
杂志文章abstract：:The qualitative and quantitative effects of the (+)-S and (-)-R enantiomers and of the racemic mixture of the Ca2+ channel antagonist, nicardipine, were compared on the isolated porcine coronary artery with intact and removed endothelium. All three forms of nicardipine inhibited the contractions induced by KCl (5-90 m...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(99)00049-7
更新日期：1999-03-12 00:00:00
abstract：:Antibodies against the neurite outgrowth inhibitor Nogo-A enhance axonal regeneration following spinal cord injury. However, antibodies directed against myelin components can also enhance CNS inflammation. The present study was designed to assess the efficacy of DNA vaccination for generating antibodies against Nogo-A...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.04.026
更新日期：2008-06-24 00:00:00
abstract：:Intravenous injection of the synthetic TRH analog, MK-771, to anesthetised cats raised the blood pressure by a central mechanism, i.e. by activating the outflow of sympathetic stimuli from the CNS to the periphery and raising the plasma concentration of adrenaline and noradrenaline. In contrast, noradrenaline in the C...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90358-5
更新日期：1988-09-01 00:00:00
abstract：:Tissue neutrophils, human salivary neutrophils donated from healthy subjects and synovial fluid neutrophils collected from patients with rheumatoid arthritis were compared with circulating blood neutrophils. Concomitant treatment of circulating blood neutrophils with tumor necrosis factor-alpha (TNF-alpha) and cyclohe...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01480-7
更新日期：2001-12-14 00:00:00
abstract：:The effects of chronic exposure to moderate levels of carbon monoxide (CO) upon the augmentation of arteriosclerotic plaque development were investigated in a series of in vivo studies. Cockerels were exposed to carefully regulated CO levels in dynamic exposure chambers. The plaque volume percentage in the aortic wall...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0926-6917(92)90025-8
更新日期：1992-09-01 00:00:00
abstract：:We now describe the preparation and characterization of a novel radioligand, 2-[125I]iodo-5-methoxy-carbonylamino-N-acetyltryptamine (2-[125I]MCA-NAT), with high affinity and pharmacological selectivity for melatonin ML2 receptor sites. 2-[125I]MCA-NAT was prepared by introducing an [125I]iodine molecule on carbon 2 o...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(95)00870-5
更新日期：1996-04-22 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：:Cocaine and a cocaine analog, WIN 36,065-2, were administered daily for 3 or 4 days. Both compounds developed sensitization to their locomotor stimulatory effects, with similarly shaped dose-response curves. Dosages giving optimal sensitization were 25 mg/kg per day for cocaine and 3 mg/kg for WIN 35,065-2. At 40 mg/k...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(86)90184-6
更新日期：1986-10-14 00:00:00
abstract：:Nerisopam, an anxiolytic and antipsychotic homophthalazine induces rapid, intense expression of Fos-like immunoreactivity in the rostral, dorsomedial and lateral parts of the striatum in the rat. Fos-positive cells also occurred in the globus pallidus, the olfactory tubercle and in the accumbens nucleus (in the cone a...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(97)01008-x
更新日期：1997-07-16 00:00:00
abstract：:The use of "multimodal" combination analgesic therapies or novel single molecules possessing multiple analgesic targets is becoming increasingly attractive. In previous experiments we showed that a substance P antagonist injected intrathecally potentiated the antinociceptive effects of potent opioid receptor agonist, ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2004.02.023
更新日期：2004-03-19 00:00:00
abstract：:In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination wit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90087-x
更新日期：1981-07-17 00:00:00
abstract：:Studies were done to assess the effects of 4-aminopyridine (4AP) and streptomycin (SM) on transmitter release parameters and extracellularly recorded presynaptic action potential. The application of 5 micrometer 4AP resulted in a marked increase in the mean quantal content (m1) associated with an increase in the total...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(81)90002-9
更新日期：1981-11-19 00:00:00
abstract：:The effect of omeprazole, a proton pump inhibitor, on the forward passage of the crop contents of chicks receiving 20% medium chain or long chain triacylglycerol was studied. Medium chain triacylglycerol significantly delayed the crop emptying of chicks compared with long chain triacylglycerol. Omeprazole also signifi...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)00684-y
更新日期：1995-01-24 00:00:00
abstract：:The responsiveness of the guinea-pig esophageal muscularis mucosae to arachidonic acid (AA) and its cyclooxygenase and lipoxygenase metabolites was examined in vitro. AA (0.1-30 microM) produced a concentration-dependent contraction of the muscularis mucosae (mean EC50 +/- S.E.M. = 5.1 +/- 1.0 microM). The contraction...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(85)90519-9
更新日期：1985-08-07 00:00:00
abstract：:To assess the role of the alpha 7 neuronal nicotinic acetylcholine receptor in the discriminative stimulus properties of (-)-nicotine, this study investigated the ability of the alpha 7 receptor antagonist methyllycaconitine to modulate the nicotine cue. In rats trained to discriminate (-)-nicotine from saline, intrap...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(96)00010-6
更新日期：1996-04-22 00:00:00
abstract：:Three important features must be considered when proposing therapeutic strategies in liver cirrhosis: inflammation, oxidative stress and fibrogenesis. Pirfenidone is a synthetic molecule which oxidative action has not been tested in cirrhosis. Cirrhosis was induced in rats by ligation of the common bile duct or carbon...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2008.06.110
更新日期：2008-10-24 00:00:00
abstract：:Cytotrienin A, a member of the triene-ansamycin family, was initially identified to be an inducer of apoptosis and recently shown to be an inhibitor of translation that interferes with eukaryotic elongation factor 1A function. In human lung carcinoma A549 cells, cytotrienin A was found to inhibit more strongly the cel...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2011.05.072
更新日期：2011-09-30 00:00:00
abstract：:TL-99 and 3-PPP, two putative dopamine autoreceptor agonists, effectively suppressed serum prolactin (PRL) concentrations in rats treated with alpha-methyltyrosine. In addition, the secretion of PRL from anterior pituitary tissue under in vitro conditions was significantly inhibited by TL-99 and 3-PPP. These findings ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(83)90565-4
更新日期：1983-06-17 00:00:00
abstract：:The effects of trichokonin VI (= gliodeliquescin A), a peptaibol isolated from the culture broth of Trichoderma koningii Oudemans, on L-type Ca2+ channel currents in single bullfrog atrial cells were investigated. Our results showed that trichokonin VI is a new potent agonist of L-type Ca2+ channels in cardiac membran...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90290-9
更新日期：1994-12-12 00:00:00
abstract：:Structurally diverse compounds have been shown to possess high affinities for benzodiazepine receptors in their 'diazepam-sensitive' (DS) conformations. In contrast, only the imidazobenzodiazepinone Ro 15-4513 has been shown to exhibit a high affinity for the 'diazepam-insensitive' (DI) conformation of benzodiazepine ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0922-4106(92)90040-3
更新日期：1992-01-14 00:00:00
abstract：:Exosomes are membrane-derived vesicles and play a critical role in cell signaling by transferring RNAs and proteins to target cells through fusion with the cell membrane. Long non-coding RNA-small nucleolar RNA host gene 9 (lncRNA-SNHG9) was proven to be an important element in lncRNA-mRNA interaction networks during ...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2020.172977
更新日期：2020-04-05 00:00:00
abstract：:The antinociceptive profile of selected histamine H(2) and histamine H(3) receptor antagonists led to the discovery of improgan, a non-brain-penetrating analgesic agent which does not act on known histamine receptors. Because no chemical congener of improgan has yet been discovered which has both antinociceptive and b...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2005.08.040
更新日期：2005-10-17 00:00:00
abstract：:The mouse and tissues from this species are increasingly used as experimental models because of the wide variety of gene deletions and overexpressions available in this species. Yet, very little is known about normal vascular responses in the mouse. We investigated the vasorelaxant responses on thoracic aortic rings f...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/s0014-2999(01)01418-2
更新日期：2001-11-16 00:00:00
abstract：:Selective serotonin reuptake inhibitors (SSRIs) are widely used as a first-line therapy in postpartum depression. The objective of this study was to determine the mechanism underlying the inhibitory effects of the SSRI, fluvoxamine, on β-casein expression, an indicator of lactation, in MCF-12A human mammary epithelial...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.09.038
更新日期：2015-11-05 00:00:00
abstract：:The effects of alpha 2-adrenoceptor and GABA receptor agonists on citric acid-induced cough and increased tidal volume were investigated in conscious guinea pigs. Inhalation of low doses of B-HT 920 (5-allyl-2-amino 5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine dihydrochloride), and xylazine significantly inhibited cit...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90747-r
更新日期：1992-09-22 00:00:00
abstract：:CP-96,345, a non-peptide, selective tachykinin NK1 receptor blocker and its inactive enantiomer, CP-96,344, inhibit ligand binding of phenylalkylamine but not dihydropyridine Ca2+ channel antagonists. Whether these Ca2+ channel antagonist properties of CP-96,345 and CP-96,344 can be expressed as cardiovascular effects...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(94)90173-2
更新日期：1994-02-11 00:00:00
abstract：:This review provides a comprehensive analysis of the anticancer potential of the natural product citral (CIT) found in many plants and essential oils, and extensively used in the food and cosmetic industry. CIT is composed of two stereoisomers, the trans-isomer geranial being a more potent anticancer compound than the...
journal_title：European journal of pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.ejphar.2020.172945
更新日期：2020-03-15 00:00:00
abstract：:The pharmacological profile of the opioid antagonist norbinaltorphimine has been characterised in vitro and in vivo. In vitro, norbinaltorphimine reversibly antagonised the effects of kappa agonists with pA2 values of 10.2-10.4. Norbinaltorphimine was much less potent as an antagonist at mu and delta receptors, pA2 va...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(87)90397-9
更新日期：1987-12-15 00:00:00
abstract：:The vasodepressor actions of the cyclic endoperoxides PGG2 and PGH2 were compared with those of their products PGD2 and PGE2 using anaesthetised normotensive and genetically hypertensive rats. Given into the aortic arch of normotensives PGE2 was approximately 6 times more potent than PGH2 and 11 times more potent tha...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(76)90133-3
更新日期：1976-10-01 00:00:00
abstract：:The effects of beta-chlornaltrexamine (CNA, 5 mg/kg s.c.) on social conflict analgesia and brain opioid binding were investigated in mice at different times after the administration of the alkylating antagonist. The specific binding of [3H]etorphine to high-affinity binding sites and the stress-induced analgesia of at...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(88)90525-0
更新日期：1988-10-18 00:00:00
