Abstract:
:The binding of agonists and antagonists to alpha 2-adrenergic receptors of human platelets was studied. The receptors showed homogeneous affinities for antagonists but two affinity states for the agonist (-)-epinephrine, which were modulated by guanine nucleotides. Van't Hoff plots of antagonist binding had a break point at about 18 degrees and considerable diversity between 18 degrees and 0 degree. Agonist binding to both affinity states showed a similar break point; agonist binding to the high affinity state was characterized by a large entropy component compared to the low affinity state. This entropy component was reduced at higher concentrations of sodium, indicating that it may be due to liberation of sodium ions. Measurements of the fluorescence of 1-anilin-8-naphthalenesulfonate showed thermotropic phase transitions of the platelet membranes at about 17 degrees. The transition temperature was decreased to about 12 degrees by addition of 10 mM octanoic acid. Octanoic acid also shifted the break points of the van't Hoff plot of antagonist and low affinity agonist binding from 18 degrees to 12 degrees. High affinity agonist binding, however, remained unchanged. It is concluded that agonist-specific thermodynamic characteristics of ligand binding to alpha 2-receptors of human platelets can only be investigated by regarding differences between high and low affinity agonist binding. These differences include an entropy increase upon ligand binding, which is in part due to enhanced liberation of sodium ions, and a loss of sensitivity to fluidity changes in the outer layer of the plasma membrane.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Lohse MJ,Klotz KN,Schwabe Usubject
Has Abstractpub_date
1986-03-01 00:00:00pages
228-34issue
3eissn
0026-895Xissn
1521-0111journal_volume
29pub_type
杂志文章abstract::Stimulation of beta2-adrenoceptors with the selective beta2 agonist procaterol caused a biphasic decrease in cell surface M2 muscarinic receptor number in human embryonic lung 299 cells when measured with the hydrophilic antagonist [3H]N-methylscopolamine. In contrast, total muscarinic receptor number, measured with t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::Analysis of the distribution of mRNA encoding the serotonin (5-hydroxytryptamine) 5-HT(2A) receptor and the mu opioid peptide receptor in rat brain demonstrated their coexpression in neurons in several distinct regions. These regions included the periaqueductal gray, an area that plays an important role in morphine-in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.048272
更新日期:2008-11-01 00:00:00
abstract::The mechanisms underlying mastoparan-induced elevation of the intracellular free calcium concentration ([Ca2+]i) were investigated in the insulin-secreting cell lines RINm5F and HIT. In both cell types, micromolar concentrations of mastoparan induced a prompt increase of [Ca2+]i, measured as an increase in fura-2 fluo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::A recently isolated monoclonal antibody was found to be a potent and powerful inhibitor of the catalytic activity of rabbit brain acetylcholinesterase (AChE; acetylcholine acetylhydrolase, EC 3.1.1.7), with an IC50 of about 1 nM and a maximal inhibition of at least 90%. The antibody increased the optimal concentration...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-12-01 00:00:00
abstract::Activation of muscarinic cholinergic receptors of 1321N1 human astrocytoma cells attenuates cyclic AMP accumulation. This effect results from an activation of phosphodiesterase with no direct inhibition of adenylate cyclase activity. In spite of this lack of coupling of muscarinic receptors to adenylate cyclase, guani...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract::Poly(A)+ RNA from mammalian retina expresses bicuculline/baclofen-insensitive gamma-aminobutyric acid (GABA) receptors in Xenopus oocytes with properties similar to those of homooligomeric GABA rho 1 receptors. The pharmacological profile of these rho-like receptors was extended by measuring sensitivities to various G...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::The dissociation constants (Kd values) of substance P (SP), physalaemin, kassinin, and SP analogues acting on SP receptors in guinea pig ileal longitudinal muscle strips were determined by the pharmacological procedures of Furchgott [Adv. Drug Res. 3:21-55 (1966)]. This method involves analysis of the concentration-re...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Molecular cloning of the alpha 2A-adrenergic receptor has shown that this receptor is a member of the gene superfamily of guanine nucleotide-binding protein (G protein)-coupled receptors. The alpha 2A-adrenergic receptor expressed in Chinese hamster ovary (CHO) cells attenuates and potentiates forskolin-stimulated cAM...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-08-01 00:00:00
abstract::Electron affinities, approximated by lowest unoccupied molecular orbital (LUMO) energies, were determined for an extensive group of nitrated polycyclic aromatic hydrocarbons by ab initio methods at the STO-3G level. Significant correlations were demonstrated between nitroarene LUMO energy and the corresponding mutagen...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-06-01 00:00:00
abstract::A high cytoplasmic Na(+) concentration may contribute to N-methyl-D-aspartate (NMDA)-induced excitotoxicity by promoting Ca(2+) influx via reverse operation of the Na(+)/Ca(2+) exchanger (NaCaX), but may simultaneously decrease the electrochemical Ca(2+) driving force by depolarizing the plasma membrane (PM). Digital ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.56.3.619
更新日期:1999-09-01 00:00:00
abstract::We have investigated the effect of chronic flurazepam HCl treatment on the gamma-aminobutyric acid (GABA)A receptor complex in cultured mammalian cortical neurons. Chronic flurazepam (1-5 microM, for 1-10 days) treatment did not produce any changes in the morphological appearance or the cell protein content of cortica...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Serotonin [5-hydroxytryptamine (5-HT)] receptors are distinguished pharmacologically by their characteristic affinities for agonists and antagonists. Two serotonin receptors, the 5-HT2 and 5-HT1c, share a number of pharmacologic and structural properties while differing in their affinities for certain agonists and ant...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Specific toxic and biochemical responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in human thymic epithelial (TE) cells in culture are mediated by the TCDD receptor protein. Characterization of the physicochemical properties of the TCDD receptor in cytosol fractions from cultured human TE cells indicates...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Isoproterenol increases and decreases contractile force at low and high concentrations, respectively, through beta(2)-adrenoceptors overexpressed in transgenic mouse heart (TG4), consistent with activation of both G(s) and G(i) proteins. Using TG4 hearts, we demonstrated that epinephrine behaves like isoproterenol, bu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.5.1313
更新日期:2004-05-01 00:00:00
abstract::The ability of dopamine agonists and antagonists to compete with [3H]spiperone binding to rat striatal membrane preparations at 4, 15, 26, and 37 degrees varied markedly with temperature. Dopamine and the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene hydrobromide (ADTN) were more potent at lower...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Expression vectors were designed and constructed to achieve optimum production of two different isozymes of rat glutathione S-transferase (GST) (EC 2.5.1.18) in COS cells, for studies of drug resistance. Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyel...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.068122
更新日期:2011-04-01 00:00:00
abstract::Previous biochemical studies have demonstrated that synergy between non-nucleoside reverse transcriptase (RT) inhibitors (NNRTI) and nucleoside RT inhibitors (NRTIs) is due to inhibition by the NNRTI of the rate at which HIV-1 RT facilitates ATP-mediated excision of NRTIs from chain-terminated template/primers (T/P). ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.038596
更新日期:2008-02-01 00:00:00
abstract::Psoralen plus UVA light (PUVA) is commonly used to treat psoriasis, a common skin disorder associated with rapid proliferation of cells. PUVA exerts its antiproliferative activity through formation of DNA monoadducts and interstrand cross-links (ICLs). However, this treatment may lead to skin malignancies as a direct ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.051698
更新日期:2009-03-01 00:00:00
abstract::Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common malignancies worldwide, with low 5-year survival rates. Current strategies that block epidermal growth factor receptor (EGFR) have limited effects when administered as single agents. Targeting EGFR via intratumoral administration of phospho...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.041160
更新日期:2008-03-01 00:00:00
abstract::4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit tr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The possibility that vasoactive intestinal polypeptide (VIP) may facilitate the nicotine-mediated induction of adrenal medullary tyrosine hydroxylase (TH) was investigated with primary cultures (5-7 days in vitro) of bovine adrenal chromaffin (BAC) cells. Exposure of BAC cells to 100 microM nicotine led to only a marg...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Thymidine phosphorylase (TPase) is one of the key enzymes involved in the pyrimidine nucleoside salvage pathway. However, TPase also stimulates angiogenesis, and its expression correlates well with microvessel density and metastasis in a variety of human tumors. We have shown recently that 5'-O-trityl-inosine (KIN59) ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.021188
更新日期:2006-08-01 00:00:00
abstract::Nicotine biotransformation affects the smoking habits of addicted individuals and therefore their health risk. Using an improved analytical method, we have discovered that the human UDP-glucuronosyltransferase (UGT) 2B10, a liver enzyme previously unknown to conjugate nicotine or exhibit considerable activity toward a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.037093
更新日期:2007-09-01 00:00:00
abstract::Cytosolic liver acetyl-CoA:arylamine N-acetyltransferase (EC 2.3.1.5) from homozygous rapid acetylator rabbits (strain III/J) was purified to homogeneity as judged by gel filtration sodium dodecyl sulfate-polyacrylamide disc gel electrophoresis and isoelectrofocusing. The isoelectric point was estimated to be 5.2. The...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::KARs, new semisynthetic antitumor bis-indole derivatives, were found to be inhibitors of tubulin polymerization with lower toxicity than vinblastine or vincristine, used in chemotherapy. Here, we compare the effect of KARs with those of vinblastine and vincristine on cell viability, cell proliferation, and cell cycle ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.6.1235
更新日期:2001-12-01 00:00:00
abstract::We showed previously that subtypes of alpha 1-adrenergic receptors can be differentiated by selective inactivation with chlorethylclonidine (CEC) [Mol. Pharmacol. 32:505-510 (1987)] or by their affinities for the competitive antagonist WB 4101 [Nature (Lond.) 329:333-335 (1987)]. Examining eight rat tissues, the propo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Camptothecin (CPT) is an effective chemotherapeutic agent for treatment of patients with cancer. The mechanisms underlying CPT-mediated responses in cancer cells are not fully understood. MicroRNA (miRNA) play important roles in tumorigenesis and drug sensitivity. However, the interaction between camptothecin and miRN...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.076794
更新日期:2012-04-01 00:00:00
abstract::The cannabinoid field is currently an active research area. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most characterized endogenous cannabinoids (also known as endocannabinoids). These neuromodulators have been implicated in various physiologically relevant phenomena, including mood (Witkin et al., 20...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.109.055251
更新日期:2009-07-01 00:00:00
abstract::The aptamer mechanism of action involves the direct interaction of oligonucleotide with protein and is responsible for the biological effects of many pharmacologically active oligodeoxynucleotides. In the work reported here, we have determined the effects of aptamers on the secondary, tertiary, and quaternary structur...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00