Abstract:
:The effect of lysosomotropic agents and secretory inhibitors were compared with verapamil for their effect on the activity of doxorubicin (DOX) in multiple drug-resistant (MDR) P388 leukemia cells (P388R) and in blocking anthracycline efflux from these cells. Agents known to interact with the plasma membrane did not potentiate DOX activity in P388R cells unless these same agents were also capable of interacting with acidic compartments within the cell. The lysosomotropic detergent Triton WR-1339, for example, potentiated DOX activity in P388R cells and stimulated the net accumulation of daunorubicin (DAU) in P388R cells by inhibiting drug exodus. However, another detergent, deoxycholate, and two membrane active antibiotics, amphotericin B and filipin, had no effect on DOX activity and/or DAU efflux in P388R cells. Lysosomotropic agents such as chloroquine and secretory inhibitors such as monensin, cytochalasin B, and vinblastine all inhibited DAU efflux from P388R cells. In a MDR B16 melanoma cell line, the activity of DOX was potentiated by both verapamil and reserpine. These same two agents also inhibited melanin secretion from this same cell line. Based on these observations, we propose that secretory vesicles derived from the Golgi apparatus might be involved in the MDR phenomenon. We further suggest that drugs such as DOX might be concentrated in these acidic vesicles, where they would be released to the outside of the cell by exocytosis.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Klohs WD,Steinkampf RWsubject
Has Abstractpub_date
1988-08-01 00:00:00pages
180-5issue
2eissn
0026-895Xissn
1521-0111journal_volume
34pub_type
杂志文章abstract::Ryanodine receptors (RyRs) are intracellular membrane channels playing key roles in many Ca(2+) signaling pathways and, as such, are emerging novel therapeutic and insecticidal targets. RyRs are so named because they bind the plant alkaloid ryanodine with high affinity and although it is established that ryanodine pro...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.114.093757
更新日期:2014-09-01 00:00:00
abstract::Cyclic nucleotide analogs were used to study relaxation of pig coronary arteries and guinea pig tracheal smooth muscle in an attempt to determine the roles of cAMP- and cGMP-dependent protein kinases (cA-K and cG-K). In pig coronary artery strips, cGMP analogs were generally more effective than cAMP analogs in promoti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-10-01 00:00:00
abstract::Two newly identified, overlapping (1 bp) glucocorticoid response elements (GREs) at -759 and -773 bp in the promoter of the rat phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) gene are primarily responsible for its glucocorticoid sensitivity, rather than the originally identified -533-bp GRE. A dose-depende...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.6.1385
更新日期:2002-06-01 00:00:00
abstract::Dantrolene was recently identified as a novel inhibitor of the plasmodial surface anion channel (PSAC), an unusual ion channel on Plasmodium falciparum-infected human red blood cells. Because dantrolene is used clinically, has a high therapeutic index, and has desirable chemical synthetic properties, it may be a lead ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.010553
更新日期:2005-07-01 00:00:00
abstract::Aflatrem, a mycotoxin from Aspergillus flavus, potentiates the gamma-aminobutyric acid (GABA)-induced chloride current. This positive allosteric regulatory action of aflatrem was quantitatively studied on the GABAA receptor channel expressed in Xenopus oocytes after injection with chick brain mRNA under voltage-clamp ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Signaling by G-protein-coupled receptors is often considered a uniform process, whereby a homogeneously activated proportion of randomly distributed receptors are activated under equilibrium conditions and produce homogeneous, steady-state intracellular signals. While this may be the case in some biologic systems, the...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.115.100248
更新日期:2015-09-01 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::Obesity is now recognized as a rapidly increasing worldwide threat to health, largely as a result of causing diabetes. Thus, considerable efforts are underway in the pharmaceutical industry to find drugs to treat this condition. Target validation in various academic and industrial laboratories has revealed a number of...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.106.026104
更新日期:2006-09-01 00:00:00
abstract::Multidrug resistance-associated protein 1 (Mrp1; Abcc1) is expressed in sarcolemma of murine heart, where it probably protects the cardiomyocyte by mediating efflux of endo- and xenobiotics. We used doxorubicin (DOX), a chemotherapeutic drug known to induce oxidative stress and thereby cardiac injury, as a model cardi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.052209
更新日期:2009-05-01 00:00:00
abstract::Nicotine can enhance working memory and attention. Activation of both alpha7 and beta2(*) nicotinic acetylcholine receptors (nAChRs) in the prefrontal cortex (PFC) has been implicated in these processes. The ability of presynaptic nAChRs to modulate neurotransmitter release, notably glutamate release, is postulated to...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.046623
更新日期:2008-08-01 00:00:00
abstract::Platelet-activating factor (PAF) receptor-coupled activation of phosphoinositide-specific phospholipase C (PLC) was studied in platelets that were made refractory, by short-term pretreatments, to either PAF or thrombin. Generation of [3H]inositol triphosphate ( [3H]IP3) was monitored specifically for this purpose. [3H...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::To determine the relationship between vascular alpha 1-adrenergic receptor occupancy and receptor-coupled calcium flux, we have studied [3H]prazosin binding and l-norepinephrine-induced 45Ca efflux in cultured vascular smooth muscle cells isolated from the rabbit aorta. In a crude cellular homogenate, [3H]prazosin bou...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::The purpose of these studies was to support the hypothesis that an undiscovered cannabinoid receptor exists in brain. [(35)S]GTP gamma S binding was stimulated by anandamide and WIN55212-2 in brain membranes from both CB(1)(+/+) and CB(1)(-/-) mice. In contrast, a wide variety of other compounds that are known to acti...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::The metabotropic glutamate 5 receptor and the cannabinoid type 1 receptor are G protein-coupled receptors that are widely expressed in the central nervous system. Metabotropic glutamate 5 receptors, present at the postsynaptic site, are coupled to Gαq/11 proteins and display an excitatory response upon activation, whe...
journal_title:Molecular pharmacology
pub_type: 杂志文章,评审
doi:10.1124/mol.116.104372
更新日期:2016-11-01 00:00:00
abstract::Prenatal exposure to diethylstilbestrol (DES) is known to cause an increased susceptibility to a wide array of clinical disorders in humans. Previous studies from our laboratory demonstrated that prenatal exposure to DES induces thymic atrophy and apoptosis in the thymus. In the current study, we investigated if such ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.114.096743
更新日期:2015-05-01 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::Hepatic very-low-density lipoprotein particles (VLDL) containing full-length apolipoprotein B100 are metabolized in the blood stream to low-density lipoprotein (LDL) particles, whose elevated levels increase the risk of atherosclerosis. Statins and bile-acid sequestrants are effective LDL-lowering therapies for many p...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.2.269
更新日期:2002-02-01 00:00:00
abstract::Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.112.080432
更新日期:2012-12-01 00:00:00
abstract::Sazetidine-A has been recently proposed to be a "silent desensitizer" of alpha4beta2 nicotinic acetylcholine receptors (nAChRs), implying that it desensitizes alpha4beta2 nAChRs without first activating them. This unusual pharmacological property of sazetidine-A makes it, potentially, an excellent research tool to dis...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.108.045104
更新日期:2008-06-01 00:00:00
abstract::Bufuralol 1'-hydroxylation is a prototypical reaction catalyzed by cytochrome P450 (P450) 2D6, an enzyme known to show debrisoquine/sparteine-type genetic polymorphism in humans. In the present study we further examined the roles of several human P450 enzymes, as well as P450 2D6, in the hydroxylation of (+/-)-bufural...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::K201 (JTV-519) may prevent abnormal Ca(2+) leak from the sarcoplasmic reticulum (SR) in the ischemic heart and skeletal muscle (SkM) by stabilizing the ryanodine receptors (RyRs; RyR1 and RyR2, respectively). We tested direct modulation of the SR Ca(2+)-stimulated ATPase (SERCA) and RyRs by K201. In isolated cardiac a...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.102277
更新日期:2016-08-01 00:00:00
abstract::[This corrects the article on p. 21 in vol. 81, PMID: 21984254.]. ...
journal_title:Molecular pharmacology
pub_type: 已发布勘误
doi:10.1124/mol.115.075234err
更新日期:2016-01-01 00:00:00
abstract::The renal outer medullary potassium channel (ROMK) is expressed in the kidney tubule and critically regulates sodium and potassium balance. The physiological functions of other inward rectifying K(+) (Kir) channels expressed in the nephron, such as Kir7.1, are less well understood in part due to the lack of selective ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.059840
更新日期:2009-11-01 00:00:00
abstract::bTREK-1 K(+) channels set the resting membrane potential of bovine adrenal zona fasciculata (AZF) cells and function pivotally in the physiology of cortisol secretion. Adrenocorticotropic hormone controls the function and expression of bTREK-1 channels through signaling mechanisms that may involve cAMP and downstream ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.109.061861
更新日期:2010-03-01 00:00:00
abstract::It has been suggested that elevated cytosolic free calcium plays a key role in acetaminophen-induced cell death. The present study has examined the effect of a toxic concentration of acetaminophen on cytosolic free calcium in single mouse hepatocytes, using the dye fura-2 and video imaging fluorescence microscopy. Cyt...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-04-01 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::We have found that stypoldione, a bright red o-quinone isolated from the brown alga Stypopodium zonale, inhibits the division of sea urchin embryos in a concentration-dependent manner (IC50 approximately 2.5 X 10(-6) M). Although previous studies have shown this marine natural product to inhibit beef brain microtubule...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract::The present study was conducted to establish a pharmacological method of controlling growth of vascular smooth muscle cells (VSMC) by blocking calcium entry. In cultured rat VSMC, 1 nM platelet-derived growth factor (PDGF) induced a biphasic elevation of cytoplasmic free calcium concentration, ([Ca2+]c). The second su...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::EM-652 (SCH 57068) is a new orally active antiestrogen that demonstrates pure antagonistic effects in the mammary gland and endometrium. In vivo studies have shown that EM-652 is primarily glucuronidated at the 7-hydroxy position in rats and that the metabolite is present in the plasma of female monkeys and human subj...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.59.3.636
更新日期:2001-03-01 00:00:00
abstract::The ligand specificity of rat adenohypophyseal vasopressin receptors was directly compared to that of peripheral receptors of the V1 and V2 types. For this purpose a series of 15 recently designed vasopressin antagonists was used. The affinities of these antagonists for rat adenohypophyseal membranes were deduced from...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00