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 mediated through a competitive inhibition of enzyme activation by interaction with calmodulin or phospholipid, and Ki values of W-7 for calmodulin-dependent phosphorylation and phospholipid-dependent protein kinase were 12 microM and 110 microM, respectively. The addition of Ca2+ inhibited the binding of [3H]W-7 to phosphatidylserine but not the binding to calmodulin. The potencies of naphthalenesulfonamide derivatives as derivatives as inhibitors of Ca2+, calmodulin-dependent protein kinase were dependent on the length of the alkyl chain (C2-C10) but not on Ca2+-activated, phospholipid-dependent protein kinase. These results suggest that naphthalenesulfonamide derivatives may be more selective inhibitors of Ca2+, calmodulin-dependent protein phosphorylation than is Ca2+-activated, phospholipid-dependent protein kinase and that the mechanism of interaction between W-7 and phosphatidylserine differs from the interaction between W-7 and calmodulin. These agents are useful tools for elucidating the physiological role of Ca2+-dependent protein phosphorylation.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Tanaka T,Ohmura T,Yamakado T,Hidaka Hsubject
Has Abstractpub_date
1982-09-01 00:00:00pages
408-12issue
2eissn
0026-895Xissn
1521-0111journal_volume
22pub_type
杂志文章abstract::Herein we provide evidence for the coexpression of two distinct prostacyclin (PGI(2)) receptors (IP) on BEAS-2B human airway epithelial cells. IP receptor heterogeneity initially was suggested by the finding that the rank orders of potency of PGI(2) and three structurally similar analogs [taprostene, iloprost, 15-deox...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.110.069674
更新日期:2011-03-01 00:00:00
abstract::Most anticancer drugs have their origin in traditional medicinal plants. We describe here a flavone, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone (PMF), from the leaves of the Thai plant Gardenia obtusifolia, that has anti-inflammatory and anticancer potential. Because the nuclear factor-κB (NF-κB) pathway is linked ...
journal_title:Molecular pharmacology
pub_type: 杂志文章,收录出版
doi:10.1124/mol.110.067512
更新日期:2011-02-01 00:00:00
abstract::The endogenous bronchodilator, S-nitrosoglutathione (GSNO), increases expression, maturation, and function of both the wild-type and the DeltaF508 mutant of the cystic fibrosis transmembrane conductance regulatory protein (CFTR). Though transcriptional mechanisms of action have been identified, GSNO seems also to have...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.106.023242
更新日期:2006-10-01 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
abstract::An azido derivative of [3H2](2S, 3S)-cis-2-(diphenylmethyl)-N-((2-methoxyphenyl) methyl)-1-azabicyclo[2.2.2]octon-3-amine (CP-96,345), a potent nonpeptide antagonist of the substance P (SP) (neurokinin-1) receptor, was synthesized and shown to have an affinity for the human SP receptor similar to that of the parent co...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::The human histamine H(4)-receptor (hH(4)R) possesses high constitutive activity and, like the human H(1)-receptor (hH(1)R), is involved in the pathogenesis of type-I allergic reactions. The study aims were to explore the value of dual H(1)/H(4)R antagonists as antiallergy drugs and to address the question of whether H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.058651
更新日期:2009-11-01 00:00:00
abstract::Glutamatergic synaptic transmitters are cleared from the synaptic cleft through excitatory amino acid transporters (EAATs) that are responsible for recycling glutamate and transporting it into neurons and glial cells. To probe the structural role of the TM4b-4c loop of EAAT1 (Rattus norvegicus), each of the 57 amino a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.117.111245
更新日期:2018-07-01 00:00:00
abstract::Molecular chaperone heat shock protein 90 (HSP90) is involved in oncogenic signaling pathways including epithelial-mesenchymal transition (EMT), a key process in tumor initiation, progression, metastasis, and chemoresistance. The molecular mechanisms underlying the involvement of HSP90 in EMT are still under investiga...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.119.116137
更新日期:2019-08-01 00:00:00
abstract::The mechanisms by which bisphosphonate drugs inhibit osteoclast-mediated bone resorption are unclear. Effects of bisphosphonates on cellular enzymes, metabolic pathways, and osteoclast morphology have previously been described and could culminate in a generalized cytotoxic effect or a decreased capacity of osteoclasts...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Activation of mitogen-activated protein kinase (MAPK) is induced by adding thyrotropin-releasing hormone (TRH) to COS-7 cells cotransfected with TRH receptors and an epitope-tagged MAPK. Long term treatment of the cells with pertussis toxin has no effect on TRH-induced MAPK activation. Incubation of the cells with the...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.53.4.613
更新日期:1998-04-01 00:00:00
abstract::Microglia, as phagocytes and antigen-presenting cells in the central nervous system, are activated in such disease processes as stroke and multiple sclerosis. Because peripheral macrophages are capable of producing endocannabinoids, we have examined endocannabinoid production in a macrophage-colony stimulating factor ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.4.999
更新日期:2004-04-01 00:00:00
abstract::The toxicity of acetaminophen (4'-hydroxyacetanilide), 3,5-dimethylacetaminophen (3'-5'-dimethyl-4'-hydroxyacetanilide), and 2,6-dimethylacetaminophen (2',6'-dimethyl-4'-hydroxyacetanilide) was investigated in hepatocytes isolated from phenobarbital-pretreated rats. At a concentration of 5 mM, acetaminophen was found ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Ribavirin used in therapies against hepatitis C virus (HCV) is potentially efficient against other viruses but presents a high cytotoxicity. Several ribavirin triphosphate analogs modified on the ribose moiety were synthesized and tested in vitro on the RNA polymerases of HCV, phage T7, and HIV-1 reverse transcriptase...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.63.3.538
更新日期:2003-03-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) was found to activate protein kinases under cell- and nucleus-free conditions in isolated C57 mouse liver cytosol (100,000 x g supernatant). This action of TCDD was found to be aryl hydrocarbon receptor (AHR) dependent, concentration dependent, and inhibited by genistein, a t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.52.4.667
更新日期:1997-10-01 00:00:00
abstract::Carbachol is 100 times more potent for inhibiting cyclic AMP formation than for stimulating phosphoinositide (PI) hydrolysis in chick heart cells. To determine whether this reflects differences in agonist affinity of the receptor(s) coupled to the two responses, we measured these functional responses following removal...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::Microglial activation is an invariant feature of Alzheimer's disease (AD). It is noteworthy that cannabinoids are neuroprotective by preventing β-amyloid (Aβ)-induced microglial activation both in vitro and in vivo. On the other hand, the phytocannabinoid cannabidiol (CBD) has shown anti-inflammatory properties in dif...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.071290
更新日期:2011-06-01 00:00:00
abstract::The phosphorylation of μ-opioid receptors (MOPRs) by G protein-coupled receptor kinases (GRKs), followed by arrestin binding, is thought to be a key pathway leading to desensitization and internalization. The present study used the combination of intracellular and whole-cell recordings from rats and mice, as well as l...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.111.076208
更新日期:2012-03-01 00:00:00
abstract::α-Conotoxins are subtype-selective nicotinic acetylcholine receptor (nAChR) antagonists. Although potent α3β2 nAChR-selective α-conotoxins have been identified, currently characterized α-conotoxins show no or only weak affinity for α4β2 nAChRs, which are, besides α7 receptors, the most abundant nAChRs in the mammalian...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.078683
更新日期:2012-10-01 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::Thiourea, phenylthiourea, and methimazole perfused into rat liver stimulated the biliary efflux of GSSG without affecting the excretion of GSH into either the bile or the caval perfusate. The thiocarbamide moiety appears essential, since perfusion with urea, phenylurea, or N-methylimidazole did not stimulate GSSG rele...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1984-07-01 00:00:00
abstract::Catecholamine transporters constitute the biological targets for several important drugs, including antidepressants, cocaine, and related compounds. Some information exists about discrete domains of these transporters that are involved in substrate translocation and uptake blockade, but delineation of domains mediatin...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.6.1404
更新日期:2000-12-01 00:00:00
abstract::We reported previously the formation of a glutathionyl conjugate of the active metabolite (AM) of clopidogrel and the covalent modification of a cysteinyl residue of human cytochrome P450 2B6 in a reconstituted system (Mol Pharmacol 80:839-847, 2011). In this work, we extended our studies of the metabolism of clopidog...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.079061
更新日期:2012-08-01 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::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::The action of tetrahydroaminoacridine (THA), a centrally active cholinesterase inhibitor that may provide symptomatic benefit in Alzheimer's disease, was studied on responses to the excitatory amino acid N-methyl-D-aspartate (NMDA) in cultured hippocampal neurons, using whole-cell voltage-clamp and single-channel reco...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::We used transcript-specific oligonucleotides to examine the localization in the rat nervous system of the corresponding mRNAs for the two P2X purinoceptor genes cloned recently from the rat vas deferens and PC12 cells. PC12 P2X purinoceptor mRNA was labeled in the olfactory tubercle, striatum, hypothalamus, hippocampu...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-10-01 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::Ethanol-inducible CYP2E1 is an enzyme of major toxicological interest because it metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. CYP2E1 has also been implicated in alcohol liver disease because of its contribution to oxidative stress. Previously, polymorphic alleles with mutations in i...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Barbiturate-induced anesthesia is a complex mechanism that probably involves several ligand-gated ion channel superfamilies. One of these superfamilies includes the archetypical nicotinic acetylcholine receptor (nAChR), in which barbiturates act as noncompetitive antagonists. In this regard, we used the Torpedo califo...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-09-01 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