Abstract:
:We have used two experimental approaches--receptor inactivation with an irreversible antagonist and changes in receptor expression during passage of cells through the cell cycle--to explore the relationship between beta-adrenergic receptor number and response in intact S49 lymphoma cells. beta-Receptors in asynchronous cultures of S49 cells were blocked to varying degrees with the irreversible antagonist bromoacetylalprenololmenthane (BAAM). Blockade by BAAM was noncompetitive and did not alter the affinity of receptors for the agonist isoproterenol. Intracellular accumulation of cAMP in response to 1 microM isoproterenol was proportional to receptor number both at times of initial and maximal accumulation. In contrast, when intracellular accumulation of cAMP in response to isoproterenol was measured in synchronized cultures of S49 cells (obtained by centrifugal elutriation), a notably different relationship was observed. Cells were least responsive, that is, receptors appeared "uncoupled," during S phase of the cell cycle. This attenuation of response was not due to alterations of receptor number, receptor affinity for agonist, or expression of the catalytic unit of adenylate cyclase. Use of the antibiotic mycophenolic acid, a selective inhibitor of the synthesis of GTP, elicited response patterns in asynchronous cells similar to those seen in synchronized cells. These results confirm that wild-type S49 cells do not possess spare receptors. In addition to the importance of total receptor number in determining maximal response to isoproterenol, receptors may show differential efficacy in promoting cAMP accumulation as cells traverse the cell cycle. Changes in cellular levels or utilization of GTP during the cell cycle may serve to regulate the coupling of receptors to the stimulation of adenylate cyclase.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Mahan LC,Insel PAsubject
Has Abstractpub_date
1986-01-01 00:00:00pages
16-22issue
1eissn
0026-895Xissn
1521-0111journal_volume
29pub_type
杂志文章abstract::The effects of alpha 2-adrenergic receptors are usually attributed to inhibition of adenylyl cyclase through pertussis toxin-sensitive Gi coupling. In kidney distal convoluted tubule (DCT) cells, stimulation of Na+/K(+)-ATPase by alpha 2 receptors involves activation of protein kinase C (PKC). To identify the signal p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::In PC12 cells stably expressing alpha(1A)-adrenergic receptors (ARs), norepinephrine (NE) activates several mitogen-activated protein kinase pathways and causes differentiation (). Using retroviral luciferase reporters, we found that NE also activated both signal transducers and activators of transcription (Stat) and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-05-01 00:00:00
abstract::4-Methyl-5-(2-pyrazinyl)-1,2-dithiole-3-thione (oltipraz), a prototype drug candidate containing a 1,2-dithiole-3-thione moiety, has been widely studied as a cancer chemopreventive agent. Oltipraz and other novel 1,2-dithiole-3-thione congeners have the capability to prevent insulin resistance via AMP-activated protei...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.051128
更新日期:2009-01-01 00:00:00
abstract::We searched for sites on the alpha-subunit of the fast Na(+) channel responsible for the difference in GTX (grayanotoxin) sensitivity of the skeletal- and cardiac-muscle Na(+) current. cDNA clones, encoding the skeletal or cardiac isoforms of the alpha-subunit, were inserted into a mammalian expression vector and tran...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Sulfation is an important pathway in the biotransformation of many drugs, xenobiotic compounds, neurotransmitters, and hormones. The sulfate donor for these reactions is 3'-phosphoadenosine-5'-phosphosulfate (PAPS). We set out to determine whether PAPS might serve as a photoaffinity ligand for sulfotransferase enzymes...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::A fusion protein consisting of the endothelin B (ET(B)) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ET(B) receptor. The ET(B) receptor and the ET(B)/...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-06-01 00:00:00
abstract::A site-directed alkylating agent was used to inactivate one or more types of opioid receptor in two bioassay preparations in the presence of type-selective ligands as protectors of other opioid receptor types. Since the pharmacological potency of an agonist is decreased when the receptor type through which it acts has...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-05-01 00:00:00
abstract::Hepatic CYP2E1 is induced in several models of alcohol administration, but clinically relevant pathology is only observed in rats in a model involving the continuous intragastric administration of an ethanol-containing, corn oil-based, high-fat diet. The level of CYP2E1 correlates with the degree of liver pathology in...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.51.6.944
更新日期:1997-06-01 00:00:00
abstract::Poly(ADP-ribose) polymerase-1 (PARP-1) is a NAD-consuming enzyme with an emerging key role in epigenetic regulation of gene transcription. Although PARP-1 expression is characteristically restricted to the nucleus, a few studies report the mitochondrial localization of the enzyme and its ability to regulate organelle ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.070110
更新日期:2011-06-01 00:00:00
abstract::The Notch family consists of four highly conserved transmembrane receptors. The release of the active intracellular domain requires the enzymatic activity of γ-secretase. Notch is involved in embryonic development and in many physiologic processes of normal cells, in which it regulates growth, apoptosis, and different...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/molpharm.120.000006
更新日期:2020-11-01 00:00:00
abstract::Notch-1 (Notch) is a cell surface receptor that regulates cell-fate decisions in the developing nervous system, and it may also have roles in synaptic plasticity in the adult brain. Binding of its ligands results in the proteolytic cleavage of Notch by the γ-secretase enzyme complex, thereby causing the release of a N...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.071076
更新日期:2011-07-01 00:00:00
abstract::Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are members of the phospholipid growth factor family. A major limitation in the field to date has been a lack of receptor subtype-specific agonists and antagonists. Here, we report that dioctylglycerol pyrophosphate and dioctylphosphatidic acid are selectiv...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::We previously demonstrated that murine bone marrow stromal cells express high levels of cytochrome P4501B1 (CYP1B1) that metabolizes 7,12-dimethylbenza[a]anthracene (DMBA), and that DMBA activates the Ah receptor (AhR) in these cells in vitro. More recently, we reported that CYP1B1 is required for DMBA-induced lymphob...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.56.6.1317
更新日期:1999-12-01 00:00:00
abstract::An 'epoxygenase' eicosanoid analog, 14, 15-cis-episulfide-eicosatrienoic acid, has several unique pharmacological effects on platelets. These include (i) inhibition of ionophore A23187- but not thrombin-induced activation, (ii) inhibition of thromboxane B2 biosynthesis derived from endogenous but not exogenous arachid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
abstract::Studies in vertebrate neuromuscular synapses have revealed previously that ATP, via P2Y receptors, plays a critical role in regulating postsynaptic gene expressions. An equivalent regulatory role of ATP and its P2Y receptors would not necessarily be expected for the very different situation of the brain synapses, but ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.066506
更新日期:2010-12-01 00:00:00
abstract::Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidy...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.097758
更新日期:2015-08-01 00:00:00
abstract::In the human lymphocyte, desensitization of the beta-adrenergic receptor-adenylate cyclase complex is associated with sequestration of the receptor as well as a change in photolabeling of beta-receptor proteins. Thus, desensitization of the lymphocyte beta-adrenergic receptor-adenylate cyclase system is associated wit...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-11-01 00:00:00
abstract::Trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ENT) family. We report here the cloning and in-depth characterization of one T. brucei brucei ENT member, TbNT9/AT-D. This transporter was expressed in Saccharomyces cerevisiae and displayed a uniquely high affini...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.031559
更新日期:2007-03-01 00:00:00
abstract::Tumors provide an extremely abnormal microenvironment that stimulates neovascularization from surrounding vessels and causes altered gene expression within vascular cells. Up-regulation of vascular endothelial growth factor (VEGF) receptors has allowed selective destruction of tumor vessels by administration of a chim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.015628
更新日期:2005-12-01 00:00:00
abstract::Pregnanolone [5 beta-pregnan-3 alpha-ol-20-one (5 beta 3 alpha)] and allopregnanolone [5 alpha-pregnan-3 alpha-ol-20-one (5 alpha 3 alpha)] are neuroactive steroids that are reduced metabolites of progesterone. Both 5 beta 3 alpha and 5 alpha 3 alpha are potent positive modulators of the gamma-aminobutyric acid respon...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Chronic morphine treatment has been shown to produce constitutive activation of mu-opioid receptors, and this transition might contribute to the development of tolerance and dependence. The apparent ability of chronic morphine to increase the spontaneous, agonist-independent activation of mu-opioid receptors may be un...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.60.1.53
更新日期:2001-07-01 00:00:00
abstract::The role of mitogen-activated protein kinase signaling and the transcription factor c-Jun in epidermal growth factor (EGF)-induced expression of 12-lipoxygenase in human epidermoid carcinoma A431 cells was studied. EGF increased the activation of extracellular signal-regulated kinase (ERK) and c-Jun amino terminal kin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::We previously described the development of genetic models to study the in vivo functions of the hepatic cytochrome P450 (P450) system, through the hepatic deletion of either cytochrome P450 oxidoreductase [POR; HRN (hepatic reductase null) line] or cytochrome b(5) [HBN (hepatic cytochrome b(5) null) line]. However, HR...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.084616
更新日期:2013-06-01 00:00:00
abstract::All-trans-retinoic acid (atRA) is the active metabolite of vitamin A. atRA is also used as a drug, and synthetic atRA analogs and inhibitors of retinoic acid (RA) metabolism have been developed. The hepatic clearance of atRA is mediated primarily by CYP26A1, but design of CYP26A1 inhibitors is hindered by lack of info...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.072413
更新日期:2011-08-01 00:00:00
abstract::Bovine pulmonary artery endothelial (CPAE) cells respond to bradykinin, and it has been suggested that the receptors on these cells do not fall into the normal B1/B2 classification of bradykinin receptors [J. Pharmacol. Exp. Ther. 244:646-649 (1988)]. The present study describes a detailed characterization of the subt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) and their class II G protein-coupled receptors VPAC(1), VPAC(2), and PAC(1) play important roles in human physiology. No small molecule modulator has ever been reported for the VIP/PACAP receptors, and ther...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.060137
更新日期:2010-01-01 00:00:00
abstract::Proliferation of activated T cells and CD56 bright natural killer (Cytokine Growth Factor Rev 13:169-183, 1995) cells caused by interleukin-2 (IL-2) has been exploited in IL-2-based therapies for the treatment of metastatic renal cell carcinoma and melanoma (J Clin Oncol 13:688-696, 1995; J Clin Oncol 17: 2105-2116, 1...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.66.4.
更新日期:2004-10-01 00:00:00
abstract::Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100693
更新日期:2016-01-01 00:00:00
abstract::Neurotrophins are a family of secreted proteins that play an important role in the development, differentiation, and survival of neurons. Studies also suggest that aberrant neurotrophin signaling may play a role in processes underlying disease states such as schizophrenia, Alzheimer's disease, and depression. Whereas ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.020255
更新日期:2006-04-01 00:00:00
abstract::A method was developed to measure the formation of glutathione adducts of 1-chloro-2,4-dinitrobenzene (CDNB) and 2,4-dichloro-1-nitrobenzene (DCNB) in periportal and pericentral regions of the liver lobule in the isolated perfused rat liver by surface reflectance spectrophotometry. Conjugates of DCNB and CDNB are rele...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00