Abstract:
:Drug-specific antibody fragments can enhance the elimination of some drugs by redistributing drug from tissues into serum and allowing renal excretion of the drug-antibody complex. This approach could potentially be used to enhance the elimination of compounds such as polychlorinated biphenyls that have very long elimination half-lives. As a first step in testing this hypothesis, the effects of 2,2',4,4',5,5'-hexachlorobiphenyl (HCB)-specific antibodies and their corresponding Fab fragments on HCB disposition were studied in rats. Antibodies to HCB were produced in chickens, and the corresponding Fab fragments were produced by digestion with papain. To study antibody effects on HCB distribution, [14C]HCB (0.1 mg) was administered i.v. to rats. Two weeks later, after distribution to tissues was complete, anti-HCB IgG or control IgG was administered i.v. The serum radiolabel concentration 2 hr after IgG administration increased 185 +/- 64% in animals treated with specific antibody vs 51 +/- 19% in control animals (P < 0.001). The increase in serum radiolabel concentration was apparent within 30 min and maximal at 2 hr. To study effects on HCB excretion, anti-HCB or control Fab fragment was administered 2 weeks after [14C]HCB. Urinary HCB excretion over the next 24 hr, measured by gas chromatography, was 10-fold greater in the group treated with anti-HCB Fab (P < 0.01). These data demonstrate that anti-HCB IgG can redistribute HCB rapidly from tissues into serum and that anti-HCB Fab can enhance urinary HCB excretion. While the magnitude of these changes was small, the data suggest that increasing HCB excretion using drug-specific antibody fragments is feasible, and can serve as a model for enhancing the excretion of compounds that have very long elimination half-lives.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Keyler DE,Goon DJ,Shelver WL,Ross CA,Nagasawa HT,St Peter JV,Pentel PRdoi
10.1016/0006-2952(94)90055-8subject
Has Abstractpub_date
1994-08-17 00:00:00pages
767-73issue
4eissn
0006-2952issn
1873-2968pii
0006-2952(94)90055-8journal_volume
48pub_type
杂志文章abstract::Most studies have reported an up-regulation of retinoic acid receptor (RAR) mRNA expression by all-trans retinoic acid (RA). We aimed to study the effect of RA on RAR protein levels in MCF-7 human breast cancer cells. Incubation of these cells with 10(-6) M RA induced a rapid breakdown of both RARalpha and RARgamma in...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00600-1
更新日期:2001-06-01 00:00:00
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journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
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更新日期:2003-03-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90304-7
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abstract::HM74 and HM74a have been identified as receptors for niacin. HM74a mediates the pharmacological anti-lipolytic effects of niacin in adipocytes by reducing intracellular cyclic AMP (cAMP) and inhibiting release of free fatty acids into the circulation. In macrophages, niacin induces peroxisome proliferator-activated re...
journal_title:Biochemical pharmacology
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90244-1
更新日期:1982-01-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90663-5
更新日期:1986-11-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(88)90390-5
更新日期:1988-10-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
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更新日期:1996-01-26 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(83)90004-7
更新日期:1983-09-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90136-8
更新日期:1994-02-11 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90635-7
更新日期:1989-10-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(03)00391-5
更新日期:2003-08-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90417-9
更新日期:1984-05-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2012.07.018
更新日期:2012-11-15 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(97)00160-3
更新日期:1997-07-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90607-0
更新日期:1985-04-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02122-1
更新日期:1996-01-12 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90584-4
更新日期:1989-11-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90716-x
更新日期:1982-08-15 00:00:00
abstract::The treatment of rats with 10 mumoles/kg (s.c.) of mercuric chloride (Hg2+) caused time-dependent decreases in the activities of the enzymes of the glutathione (GSH) metabolism pathway in the kidney. Twenty-four hours after administration of Hg2+, the activities of gamma-glutamylcysteine synthetase and glutathione dis...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90085-5
更新日期:1982-10-01 00:00:00
abstract::B-Raf kinase is the key point in a main branch of mitogen-activated protein kinase pathways and some of its mutations, such as the V600E mutation, lead to the persistent activation of ERK signaling and the trigger of severe diseases, including melanoma and other somatic cancers. Several potent drugs have been approved...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2017.02.022
更新日期:2017-05-15 00:00:00
abstract::5-Hydroxytryptamine (serotonin, 5-HT) stimulates basal adenylyl cyclase activity in membranes from guinea pig or rat hippocampi, but 5-HT inhibits forskolin-stimulated adenylyl cyclase activity in these same membranes. The opposing effects of 5-HT on adenylyl cyclase activity indicate that distinct 5-HT receptors, pos...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(90)90453-r
更新日期:1990-10-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(02)01351-5
更新日期:2002-11-01 00:00:00
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journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2020.114310
更新日期:2021-01-01 00:00:00
abstract::It is increasingly clear that some of the effects of both free and derivatised long chain fatty acids in pancreatic beta-cells are mediated by a group of G-protein coupled receptors. Some of these display close structural homology while others are more divergent. This Commentary reviews the expression and functional r...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2009.07.020
更新日期:2009-12-15 00:00:00
abstract::Cinnamaldehyde is a natural product from spices that inhibits cell separation in Bacillus cereus. Cell division is regulated by FtsZ, a prokaryotic homolog of tubulin. FtsZ assembles into the Z-ring at the site of cell division. Here, we report the effect of cinnamaldehyde on FtsZ and hence on the cell division appara...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.06.029
更新日期:2007-09-15 00:00:00
abstract::The possible role of fluroacetate in the toxicity and antitumour activity of the fluroethylnitrosoureas, BFNU and FCNU has been studied in CBA mice bearing the TLX5 lymphoma either sensitive (TLXS) or resistant (TLXRT) to nitrosoureas. Treatment of mice bearing either TLXS or TLXRT tumours with either BFNU or FCNU cau...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(85)90353-3
更新日期:1985-09-15 00:00:00
abstract::The oxidative metabolism of more than 20 drugs (e.g. sparteine, debrisoquine, dextromethorphan) is mediated by cytochrome P450IID6. Codeine O-demethylation to morphine was recently demonstrated to co-segregate with the polymorphic metabolism of debrisoquine and dextromethorphan. The female Dark-Agouti rat (DA) is an a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90077-i
更新日期:1991-03-01 00:00:00