Abstract：
BACKGROUND AND PURPOSE:Chronic nicotine exposure upregulates α4β2* nicotinic acetylcholine receptors (nAChRs) in the brain. The goal of this study was to examine the role of three serine residues in the large cytoplasmic loop of the α4 subunit on α4β2* upregulation in neurons. EXPERIMENTAL APPROACH:Serine residues S336, S470 and S530 in mouse α4 were mutated to alanine and then re-expressed in primary neurons from cortex, hippocampus and subcortex of α4 KO mice. Mutant and wild type α4 expressing neurons were treated with nicotine (0.1, 1 and 10 μM) and assessed for α4β2* upregulation. KEY RESULTS:α4β2* nAChRs expressing S336A or S470A mutants were deficient at cell surface upregulation in both subcortex and hippocampal neurons. S530A α4β2* mutants exhibited aberrant surface upregulation in subcortical neurons. None of the mutants affected surface upregulation in cortical neurons or upregulation of total α4β2* binding sites in any region. Further, dense domains or clusters of α4β2* nAChRs were observed in the neuronal surface. The impact of nicotine exposure on the intensity, area, and density of these clusters was dependent upon individual mutations. CONCLUSIONS AND IMPLICATIONS:Effects of α4 nAChR mutants on surface upregulation varied among brain regions, suggesting that the cellular mechanism of α4β2* upregulation is complex and involves cellular identity. We also report for the first time that α4β2* nAChRs form clusters on the neuronal surface and that nicotine treatment alters the characteristics of the clusters in an α4 mutant-dependent manner. This finding adds a previously unknown layer of complexity to the effects of nicotine on α4β2* expression and function.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Zambrano CA,Escobar D,Ramos-Santiago T,Bollinger I,Stitzel Jdoi
10.1016/j.bcp.2018.11.008subject
Has Abstractpub_date
2019-01-01 00:00:00pages
64-73eissn
0006-2952issn
1873-2968pii
S0006-2952(18)30477-5journal_volume
159pub_type
杂志文章abstract：:In isolated hepatic nuclei, the heavy metals Zn2+ and Cu2+ (10 microM) inhibited Ca2+ uptake and caused a prompt release of Ca2+ from preloaded nuclei in a concentration-dependent manner, with Zn2+ being more effective than Cu2+. The sulfhydryl group reducing agent dithiothreitol (DTT) protected the nuclei from the ef...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90180-5
更新日期：1993-02-24 00:00:00
abstract：:Nitric oxide (NO) and hydrogen sulfide (H2S) are two gasotransmitters that are produced in the human body and have a key role in many of the physiological activities of the various organ systems. Decreased NO bioavailability and deficiency of H2S are involved in the pathophysiology of type 2 diabetes and its complicat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.113819
更新日期：2020-06-01 00:00:00
abstract：:The present study has examined the effect of colchicine and cytochalasin B, two cytoskeleton disrupter compounds, on the formation of dopamine in slices of rat renal cortex loaded with exogenous L-3,4-dihydroxyphenylalanine (L-DOPA); the deamination of newly formed dopamine into 3,4-dihydroxyphenylacetic acid (DOPAC) ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90085-w
更新日期：1992-11-03 00:00:00
abstract：:This study investigated the role of endothelium- and smooth muscle-dependent mechanisms in the interaction of cyclosporine (CyA), an immunosuppressant drug, with beta-adrenoceptor (isoprenaline)-mediated relaxations in isolated rat aortas precontracted with phenylephrine. CyA effects were assessed in the absence and p...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.10.015
更新日期：2007-02-01 00:00:00
abstract：:Cell based studies have suggested that the diabetes drug metformin may combine with the anaplastic lymphoma kinase receptor (ALK) inhibitor crizotinib to increase ALK positive lung cancer cell killing and overcome crizotinib resistance. We therefore tested metformin alone and in combination with crizotinib in vivo, by...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114345
更新日期：2021-01-01 00:00:00
abstract：:A series of quinoline derivatives were analysed for the influence on leukotriene synthesis as a parameter for 5-LOX (EC 1.13.11.34) activity in a cell-free system of the 10,000 g supernatant of human PMNL (polymorphonuclear leukocytes). The ratios of the IC50 values for leukotriene synthesis inhibition in this cell-fr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)90264-x
更新日期：1994-06-15 00:00:00
abstract：:The effect of deferoxamine on nucleotide metabolism in HL-60 leukemic cells was studied to explore the mechanism of its antiproliferation activity. It was found that in intact cells deferoxamine markedly inhibited the ribonucleotide reduction and incorporation of bases (adenine, hypoxanthine), ribonucleosides (inosine...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90601-0
更新日期：1987-07-15 00:00:00
abstract：:The International Diabetes Federation predicts that by 2045 the number of individuals afflicted with diabetes will increase to 629 million. Furthermore, ∼352 million individuals with impaired glucose tolerance are at increased risk for developing diabetes. Several mechanisms have been proposed for the onset of metabol...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2018.04.026
更新日期：2018-08-01 00:00:00
abstract：:A set of sulfamides designed, synthesized and evaluated against maximal electroshock seizure (MES) and pentilenetetrazol (PTZ) tests with promising results, were tested for their affinity for the benzodiazepine binding site of the GABA(A) receptor. The most active compounds, N,N'-dicyclohexylsulfamide (7) and N,N'-dip...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.10.015
更新日期：2012-01-15 00:00:00
abstract：:The purpose of this study was to investigate in rats the effects of three anthracyclines, pirarubicin, doxorubicin and epirubicin on gastric prostaglandin E2 (PGE2) metabolism and phospholipase A2 (PLA2, EC 3.1.1.4) activity. The level of the membrane precursor, arachidonic acid, and the stability of the membrane were...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90509-u
更新日期：1993-08-03 00:00:00
abstract：:Mammary gland and liver microsomes of lactating rats were examined for the components of mixed function oxidase and related enzyme activities. Cytochrome b5, NADH- and NADPH- dependent cytochrome c reductase activities were 15-, 6- and 10-fold lower, respectively, in the mammary gland than in the liver microsomes. The...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90217-9
更新日期：1982-01-15 00:00:00
abstract：:Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8/IL-8) receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis. Given the unique mode of action of repertaxin it was important to examine ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.10.007
更新日期：2005-02-01 00:00:00
abstract：:Two diet-derived phenolic acids, caffeic and p-coumaric acids, interplayed with ascorbate in the protection of low density lipoproteins (LDL) from oxidation promoted by ferrylmyoglobin. Ferrylmyoglobin, a two-electron oxidation product from the reaction of metmyoglobin and H2O2, was able to oxidize LDL, degrading free...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(97)00470-x
更新日期：1998-02-01 00:00:00
abstract：:[3H]Morphine, PL-017[prolyl-3,4-3H,D-prolyl,3,4-3H] ([3H]PL-017) and enkephalin-(2-D-penicillamine,5-D-penicillamine)[tyrosyl-2,6-3H] ([3H]DPDPE) were directly cross-linked to mouse brain opiate receptors by an ultraviolet (254 nm) irradiation procedure. [3H]Morphine preferentially and specifically labeled a 58 kDa pr...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90458-9
更新日期：1993-10-05 00:00:00
abstract：:Breast cancer is the most prevalent type of tumor and the second leading cause of death due to cancer among women. Although screening methods, diagnosis and therapeutic options have improved in the last decade, chemoresistance remains an important challenge. There is evidence relating breast cancer resistance with sig...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.113959
更新日期：2020-07-01 00:00:00
abstract：:The neuroprotective effects of adenosine are well-recognized. Recently, propentofylline, a xanthine derivative, has been shown to increase extracellular concentrations of adenosine in ischemic brain and to limit the extent of neuronal damage in experimental models of cerebral ischemia. Since the concentration of adeno...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90499-m
更新日期：1993-09-01 00:00:00
abstract：:Elongator, a multi-subunit complex assembled by the IkappaB kinase-associated protein (IKAP)/hELP1 scaffold protein is involved in transcriptional elongation in the nucleus as well as in tRNA modifications in the cytoplasm. However, the biological processes regulated by Elongator in human cells only start to be elucid...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.03.006
更新日期：2008-06-01 00:00:00
abstract：:The (Na+ + K+)-ATPase is localized to the cerebral endothelium, i.e. the blood-brain barrier, and is important for the maintenance of the brain electrolyte environment. Data from the present study indicate that Pb2+ inhibits the binding of [3H]ouabain to the cerebral microvascular (Na+ + K+)-ATPase in a time- and dose...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90606-l
更新日期：1990-06-15 00:00:00
abstract：:To investigate the potential interactions between the angiotensin II (Ang II) and insulin signaling systems, regulation of IRS-1 phosphorylation and insulin-induced Akt activation by Ang II were examined in clone 9 (C9) hepatocytes. In these cells, Ang II specifically inhibited activation of insulin-induced Akt Thr(30...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.014
更新日期：2010-03-01 00:00:00
abstract：:The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90430-2
更新日期：1986-10-01 00:00:00
abstract：:Curcumin, a yellow pigment present in the Indian spice turmeric (associated with curry powder), has been linked with suppression of inflammation; angiogenesis; tumorigenesis; diabetes; diseases of the cardiovascular, pulmonary, and neurological systems, of skin, and of liver; loss of bone and muscle; depression; chron...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2008.08.008
更新日期：2008-12-01 00:00:00
abstract：:Active efflux from procaryotic as well as eucaryotic cells strongly modulates the activity of a large number of antibiotics. Effective antibiotic transport has now been observed for many classes of drug efflux pumps. Thus, within the group of primary active transporters, predominant in eucaryotes, six families belongi...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(00)00291-4
更新日期：2000-08-15 00:00:00
abstract：:The kinetics of methotrexate inhibition of dihydrofolate reductase from Neisseria gonorrhoeae have been investigated. Methotrexate was shown to be a tight-binding inhibitor (Kt = 13 pM) competitive with dihydrofolate. However, "stoichiometric" or "pseudoirreversible" inhibition could not be demonstrated. Progress curv...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90579-3
更新日期：1984-07-01 00:00:00
abstract：:Resealed synaptic plasma membrane vesicles exhibit Na+-dependent Ca2+ transport activity which may participate in regulation of free Ca2+ concentrations in nerve endings. Sodium chloride-loaded vesicles took up Ca2+ from the external medium (150 mM KCl-25 mM Tris/HCl) in the presence of an outward-directed Na+ gradien...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90612-3
更新日期：1983-03-15 00:00:00
abstract：:In this study, 1,4,6-androstatriene-3,17-dione (ATD) was demonstrated to cause time-dependent loss of aromatase activity in rat ovarian microsomes in vitro. In vivo, an injection of ATD caused inhibition of ovarian aromatase and reduced estrogen secretion in pregnant mare's serum gonadotropin-primed rats for at least ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90415-4
更新日期：1982-06-01 00:00:00
abstract：:Epilepsy is characterised by spontaneous recurrent seizures that are caused by an imbalance between neuronal excitability and inhibition. Since ion channels play fundamental roles in the generation and propagation of action potentials as well as neurotransmitter release at a subset of excitatory and inhibitory synapse...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114043
更新日期：2020-11-01 00:00:00
abstract：:A homologous series of potent, long-lasting thiazolo-pyrimidone-pyridine histamine H2-antagonists were examined for their inhibitory effects on rat hepatic ethylmorphine N-demethylation. Inhibitory potency increased in the order: 2-pyridinyl less than 3-pyridinyl less than 4-pyridinyl histamine H2-antagonist. Substitu...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90052-9
更新日期：1987-05-15 00:00:00
abstract：:The existence of a distinct pool of glutathione in the nucleus of cultured human melanoma cells was demonstrated. Melanoma cell nuclei contained 13-35 pmol of glutathione/10(6) nuclei, or approximately 0.4-1.3% of the total cellular glutathione. This nuclear glutathione pool resisted depletion by buthionine sulfoximin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(92)90540-y
更新日期：1992-10-06 00:00:00
abstract：:Human CYP2A6 is a cytochrome P450 (CYP) isoform responsible for the metabolism of nicotine, coumarin, tegafur, and valproic acid, and metabolic activation of nitrosamines. Genetic polymorphisms of the CYP2A6 gene are a major causal factor of the large interindividual differences in nicotine metabolism. In the present ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.05.029
更新日期：2005-09-01 00:00:00
abstract：:Cephaloridine and cephaloglycin are the two most nephrotoxic cephalosporins released for human use. Cephaloridine has been shown to produce both oxidative and mitochondrial respiratory injury in renal cortex in patterns of dose (or concentration) and time that are consistent with pathogenicity. Cephaloglycin also prod...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90233-5
更新日期：1989-03-01 00:00:00
