Abstract：
:Modulation of neuronal ion channels by the cloned rat brain CB1 cannabinoid receptor was investigated with the use of a heterologous neuronal expression system. Transient expression of the rat brain CB1 cannabinoid receptor was accomplished through microinjection of in vitro transcribed cRNA into the cytoplasm of enzymatically dissociated adult rat superior cervical ganglion neurons. The cannabimimetic aminoalkylindole WIN 55,212-2 inhibited whole-cell Ca2+ currents in neurons injected 16-25 hr previously with rat brain CB1 cannabinoid receptor cRNA. Inhibition of the Ca2+ current was voltage and concentration dependent, with a maximal inhibition of 73% and an IC50 value of 47 nM. The synthetic cannabinoid analogue CP55,940 also inhibited Ca2+ currents, with a maximal inhibition of 38% and an IC50 value of 7 nM. Ca2+ current inhibition was blocked by inclusion of guanosine-5'-O-(2-thiodiphosphate) in the intracellular patch pipette solution or by pretreatment with pertussis toxin. Pretreatment with the N-type Ca2+ channel antagonist omega-conotoxin GVIA reduced the inhibition by 100 nM WIN 55,212-2 from 44% to 6%, indicating that N-type Ca2+ channels are a target of cannabinoid action. On washout of WIN 55,212-2, the Ca2+ current amplitude "overrecovered" in 47% of the neurons tested. Anandamide, the endogenous cannabimimetic compound, had an inconsistent effect on the voltage-dependent Ca2+ currents in the majority of neurons microinjected with cannabinoid receptor cRNA. Ca2+ channels were a specific effector target of the cannabinoid receptor, as two different K+ currents, the M current and the A current, were not modulated by the cannabimimetic WIN 55,212-2.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Pan X,Ikeda SR,Lewis DLsubject
Has Abstractpub_date
1996-04-01 00:00:00pages
707-14issue
4eissn
0026-895Xissn
1521-0111journal_volume
49pub_type
杂志文章abstract：:The members of the Cys-loop ligand-gated ion channel (LGIC) gene family play a major role in fast synaptic transmission, and these receptors represent an important class of targets for therapeutic agents. Each member of this gene family is a pentameric complex containing one or more different subunits, and a large num...
journal_title：Molecular pharmacology
pub_type： 评论,杂志文章,评审
doi：10.1124/mol.105.020727
更新日期：2006-02-01 00:00:00
abstract：:Exchange protein directly activated by cAMP (EPAC) and cAMP-dependent protein kinase (PKA) are two intracellular receptors that mediate the effects of the prototypic second messenger cAMP. Identifying pharmacological probes for selectively modulating EPAC activity represents a significant unmet need within the researc...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.112.080689
更新日期：2013-01-01 00:00:00
abstract：:Lysosomes degrade cellular proteins and organelles and regulate cell signaling by providing a surface for the formation of critical protein complexes, notably molecular target of rapamycin (mTOR) complex 1 (mTORC1). Striking differences in the lysosomes of cancer versus normal cells suggest that they could be targets ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113118
更新日期：2019-01-01 00:00:00
abstract：:We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) iso...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:The lymphocyte potassium channel Kv1.3 is widely regarded as a promising new target for immunosuppression. To identify a potent small-molecule Kv1.3 blocker, we synthesized a series of 5-phenylalkoxypsoralens and tested them by whole-cell patch clamp. The most potent compound of this series, 5-(4-phenylbutoxy)psoralen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.65.6.1364
更新日期：2004-06-01 00:00:00
abstract：:Ethanol administration to rats by ethanol vapor inhalation (14 days) results in a 40-50% reduction in the level of gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit mRNAs [4.4 and 4.8 kilobases (kb)] in the cerebral cortex. The level of alpha 2 subunit mRNA (8.0 kb) was also reduced by 29%, whereas there was n...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
abstract：:The verapamil-like arylazide (-)-[3H]azidopamil specifically photoaffinity labeled two low molecular mass polypeptides, with apparent molecular masses of 22 and 27 kDa, in the endoplasmic reticulum of guinea pig liver, kidney, adrenal gland, and lung. It was recently shown that the 22-kDa polypeptide binds the anti-is...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) and its derivatives. Kinetic analysis indicated that the primary effect of these agents was me...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1982-09-01 00:00:00
abstract：:Activation of alpha 1-adrenergic receptors (alpha 1-AR) increases Na+/H+ exchange (NHE) in proximal tubule. NHE mediates the majority of active Na+ absorption in the proximal tubule. Three alpha 1-AR subtypes have been detected in kidney by molecular and binding techniques. We detected message for all three alpha 1-AR...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.52.6.1010
更新日期：1997-12-01 00:00:00
abstract：:The microtubule-binding taxanes, docetaxel and cabazitaxel, are administered intravenously for the treatment of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is largely hampered by their low and highly variable bioavailabilities. Using a simple, rapid, and environmentally friend...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.119.118539
更新日期：2020-06-01 00:00:00
abstract：:Neuroactive steroids have been postulated to cause anesthesia by binding to unique steroid recognition sites on gamma-aminobutyric acid (GABA) receptors and modulating GABA receptor function. Steroids interact with these sites diastereoselectively, but it is unknown whether steroid sites show enantioselectivity. To ad...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:The endocannabinoids anandamide and 2-arachidonyl glycerol (2-AG) bind to G protein-coupled central and peripheral cannabinoid receptors CB1 and CB2, respectively. Due to the relatively high expression of the CB2 isotype on peripheral immune cells, it has been hypothesized that this receptor mediates the immunosuppres...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-05-01 00:00:00
abstract：:The 2,3,7,8-tetrachlorodibenzo-p-dioxin-transformed aryl hydrocarbon receptor (AHR) complex binds to xenobiotic-responsive element (XRE) sequences in the 5' flanking region of the CYP1A1 gene, resulting in initiation of transcription. Both components of the transformed AHR complex [the ligand-binding AHR monomer and t...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Beta-L-dioxolane-cytidine (L-OddC, BCH-4556, Troxacitabine), a novel L-configuration deoxycytidine analog, is under phase III clinical trial for cancer treatment. We showed that human apurinic/apyrimidinic endonuclease (APE-1) has exonuclease activity for preferentially removing L-OddC and other L-configuration nucleo...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.021527
更新日期：2006-05-01 00:00:00
abstract：:Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique desig...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.117.111450
更新日期：2018-08-01 00:00:00
abstract：:ATP-sensitive K(+) channels are closed by the hypoglycemic sulfonylureas like glibenclamide (GBC) and activated by a class of vasorelaxant compounds, the K(+) channel openers. These channels are octamers of Kir6.x and sulfonylurea receptor (SUR) subunits with 4:4 stoichiometry. The properties of the opener-sensitive K...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
abstract：:Glyceryl trinitrate (GTN) is used in the treatment of angina pectoris and cardiac failure, but the rapid onset of GTN tolerance limits its clinical utility. Research suggests that a principal cause of tolerance is inhibition of an enzyme responsible for the production of physiologically active concentrations of NO fro...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.64.5.1109
更新日期：2003-11-01 00:00:00
abstract：:Depending on their primary structure, the 28 mammalian transient receptor potential (TRP) cation channels identified so far can be sorted into 6 subfamilies: TRPC ("Canonical"), TRPV ("Vanilloid"), TRPM ("Melastatin"), TRPP ("Polycystin"), TRPML ("Mucolipin"), and TRPA ("Ankyrin"). The TRPV subfamily (vanilloid recept...
journal_title：Molecular pharmacology
pub_type： 杂志文章,评审
doi：10.1124/mol.109.055624
更新日期：2009-06-01 00:00:00
abstract：:Very few antagonists have been identified for the human pregnane X receptor (PXR). These molecules may be of use for modulating the effects of therapeutic drugs, which are potent agonists for this receptor (e.g., some anticancer compounds and macrolide antibiotics), with subsequent effects on transcriptional regulatio...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.108.049437
更新日期：2008-09-01 00:00:00
abstract：:Identification of nonadrenergic binding sites for clonidine and related imidazolines in brain and peripheral tissues and partial purification of an endogenous ligand for these sites have led to the postulation of a novel transmitter/receptor system. The receptors seem to be present in adrenal medulla and to regulate c...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-12-01 00:00:00
abstract：:In rat pancreatic zymogen granules (ZG), an ATP-sensitive K(+) conductance and a Cl(-) conductance have been characterized that are inversely regulated by an approximately 65-kDa multidrug resistance P-glycoprotein (mdr1) gene product. In search of a label for purification of this protein, we found that the dihydropyr...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：2000-02-01 00:00:00
abstract：:Circular RNAs (circRNAs) are a distinct category of single-stranded, covalently closed RNAs formed by backsplicing. The functions of circRNAs are incompletely known and are under active investigation. Here, we report that in addition to traditional linear mRNAs (linRNA), mouse, rat, and human opioid receptor genes gen...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.118.113977
更新日期：2019-08-01 00:00:00
abstract：:We present a mechanism for agonist-promoted alpha(2A)-adrenergic receptor (alpha(2A)-AR) activation based on structural, pharmacological, and theoretical evidence of the interactions between phenethylamine ligands and alpha(2A)-AR. In this study, we have: 1) isolated enantiomerically pure phenethylamines that differ b...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.59.5.1343
更新日期：2001-05-01 00:00:00
abstract：:Ethylketocyclazocine (EKC) binds to two sites on NCB-20 neuroblastoma X Chinese hamster brain hybrid cells (KDH = 2 nM, Bmax = 21,000 sites/cell; KDL = 27 nM, Bmax = 140,000 sites/cell. The high-affinity site has been characterized as a delta opiate receptor. The low-affinity site is relatively benzomorphan-specific; ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). HL-60 cells selected in 0.05 micrograms/ml doxorubicin (DOX) are 10-fold and > 20-fold resistant to DOX and etoposide (VP-16), respectively. The accu...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:The highly conserved Arg in the so-called DRY motif (Asp-Arg-Tyr) at the intracellular end of transmembrane helix 3 is in general considered as an essential residue for G protein coupling in rhodopsin-like seven transmembrane (7TM) receptors. In the open reading frame 74 (ORF74) receptor encoded by equine herpesvirus ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.105.011239
更新日期：2005-07-01 00:00:00
abstract：:An investigation of the conformational profiles of two cyclic delta-selective opioid peptides, [D-Pen2,D-Pen5]-enkephalin and [D-Pen2,L-Pen5]-enkephalin, has been made. The methods and procedures used are more extensive and systematic than those previously reported, involving a combination of nested grid rotations, cy...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1991-04-01 00:00:00
abstract：:Thymidylate synthase (TYMS; EC 2.1.1.15) catalyzes the reductive methylation of 2'-deoxyuridine-5'-monophosphate (dUMP) by N(5),N(10)-methyhlenetetrahydrofolate, forming dTMP for the maintenance of DNA replication and repair. Inhibitors of TYMS have been widely used in the treatment of neoplastic disease. A number of ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：10.1124/mol.115.099614
更新日期：2015-12-01 00:00:00
abstract：:Previous studies indicated that activation of alpha 1-adrenergic receptors in BC3H-1 muscle cells (S. K. Ambler and P. Taylor, J. Biol. Chem. 261:5866-5871, 1986) and muscarinic receptors in 1321N1 astrocytoma cells (S. B. Masters, T. K. Harden, and J. H. Brown, Mol. Pharmacol. 27:325-332, 1985) resulted in the rapid ...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1987-09-01 00:00:00
abstract：:The functional significance of the conserved amino acids within transmembrane regions II and VII of the human 5-hydroxytryptamine (5-HT)1A receptor was analyzed by oligonucleotide-directed mutagenesis followed by transient expression of the mutated receptor genes in COS-1 cells. The substitution of a conserved asparag...
journal_title：Molecular pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
