Abstract:
:The actions of eight cationic amphiphilic drugs on human platelets displayed three different effects according to drug concentration ranges. At lower concentrations (below approximately 25 microM), the drugs stimulated secretory responses induced by 0.2 U/mL of thrombin, while at concentrations in the 25-50 microM range they inhibited these responses. Above 50-100 microM, the drugs caused permeabilization of the platelet plasma membrane as measured by leakage of cytoplasmic adenine nucleotides. The effects of these agents on phosphoinositide metabolism were monitored in platelets prelabeled with (32)P-inorganic phosphate, such that phosphatidic acid (PA), phosphatidylinositol 4-phosphate (PIP), and phosphatidylinositol 4,5-bisphosphate (PIP(2)), but not phosphatidylinositol (PI), were labeled to equilibrium. In unstimulated platelets, the level of labeled PA decreased slightly (about 25%), with corresponding increases in PIP(2) labeling up to drug concentrations of about 50 microM. In contrast to the relatively small changes in PI and PIP(2), the levels of labeled PIP, precursor to PIP(2), increased 2- to 4-fold in both resting and thrombin-treated platelets from 5 microM up to about 50-100 microM of drugs and remained elevated throughout the permeabilization concentrations. [(32)P]PA increased 20-fold over control upon thrombin activation and 5-30 microM of drugs caused [(32)P]PA to increase 30-37 times over that seen in control, resting platelets; the concentration of drugs that potentiated thrombin-induced [(32)P]PA elevation corresponded to that causing the potentiation of platelet secretion. Higher drug concentrations decreased [(32)P]PA elevation. [(32)P]PIP(2) levels increased about 25% in response to thrombin treatment alone; low concentrations of drugs led to another 25% elevation. A significant decrease in [(32)P]PIP(2) was seen above 30 microM, corresponding to inhibition of platelet secretion. Concentrations of 5-30 microM of several psychoactive agents, both neuroleptics and antidepressants, potentiated the thrombin-induced activation of platelets as measured by dense granule secretion and increased turnover of phosphoinositides. Remarkably, all of the drugs increased the levels of PIP even in resting platelets, indicating that they have common effects apart from the specific receptor interactions currently attributed to them. These common effects, e.g. an increase in membrane fluidity such as is known to be caused by amphipathic agents, may be in part responsible for the observed overlapping psychotropic effects of tricyclic antidepressants and phenothiazines.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Tharmapathy P,Fukami MH,Holmsen Hdoi
10.1016/s0006-2952(00)00445-7subject
Has Abstractpub_date
2000-11-01 00:00:00pages
1267-77issue
9eissn
0006-2952issn
1873-2968pii
S0006-2952(00)00445-7journal_volume
60pub_type
杂志文章abstract::Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological prop...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2011.11.026
更新日期:2012-02-15 00:00:00
abstract::Studies were performed to characterise the phospholipase A2 (PLA2) responsible for the greatly increased capacity to release arachidonic acid (AA) of dimethyl sulphoxide (DMSO) differentiated U937 monocytic cells compared to undifferentiated cells (18-fold increase in response to Ca2+ ionophore A23187). Cytosolic PLA2...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(95)02084-5
更新日期:1995-11-27 00:00:00
abstract::The transcription factor NF-kappaB plays a key role in a wide variety of cellular processes such as innate and adaptive immunity, cellular proliferation, apoptosis and development. In unstimulated cells, NF-kappaB is sequestered in the cytoplasm through its tight association with inhibitory proteins called IkappaBs, c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2006.06.017
更新日期:2006-10-30 00:00:00
abstract::A selected number of 1,3-diaminobenzo[f]quinazolines and 1,3-diamino-5,6-dihydrobenzo[f]quinazolines, which may be viewed as tricyclic analogues of the lipid-soluble antifolates pyrimethamine (PM), metoprine (DDMP), and etoprine (DDEP), were tested as inhibitors of purified dihydrofolate reductase (DHFR) from WI-L2 ly...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90554-6
更新日期:1989-08-15 00:00:00
abstract::In this study we compared two methods, electron spin resonance (ESR) spectroscopy and high performance liquid chromatography (HPLC), which are currently used to detect directly hydroxyl radical (OH.) formation in the ischemic and reperfused heart. Isolated buffer-perfused rat hearts were subjected to 30 min of normoth...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(93)90182-v
更新日期:1993-02-24 00:00:00
abstract::Many of the complications of diabetes seem to be due to aldose reductase (aldehyde reductase 2, ALR2) catalysing the increased conversion of glucose to sorbitol. Therapy with aldose reductase inhibitors (ARIs) could, therefore, decrease the development of diabetic complications. (2,6-Dimethylphenylsulphonyl)nitrometha...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(91)90346-7
更新日期:1991-11-06 00:00:00
abstract::The effect of naturally occurring hydroxystilbene, 3,3',4,5-tetrahydroxystilbene (piceatanol), and its derivatives on gastric H+, K(+)-ATPase was studied. Piceatanol inhibited H+, K(+)-ATPase in a dose-dependent manner. The 50% inhibition value was 4.3 x 10(-6) M. It was found from the kinetic study that the inhibitio...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90096-2
更新日期:1992-11-17 00:00:00
abstract::Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent ant...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.12.005
更新日期:2014-03-15 00:00:00
abstract::The relative ease of generation of reactive oxygen species from a series of reductively activated aglycone and sugar modified anthracyclines was compared by the extents of single strand scission in supercoiled PM2-covalently closed circular (CCC)-DNA. The electrochemical properties of these agents were used as a quant...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(82)90162-9
更新日期:1982-02-15 00:00:00
abstract::The effects of beta 1- and beta 1 + beta 2-antagonists on the myocardial adaptation to exercise training were investigated in male Sprague-Dawley rats randomly divided into trained (treadmill, 1 hr/day, 5 days/week for 10 weeks at 27 m/min, 15% grade) without drug (TC), sedentary without drug (SC), trained treated wit...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90319-4
更新日期:1987-10-15 00:00:00
abstract::Induction of the breast cancer resistance protein (BCRP/ABCG2) expression has been found in various tissues and cell-types after exposure to chemicals including 17β-estradiol, rosiglitazone, imatinib, as well as aryl hydrocarbon receptor (AhR) activators such as 2,3,7,8-tetrachlorodibenzodioxin, 3-methylcholanthrene (...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.08.016
更新日期:2010-12-01 00:00:00
abstract::We have previously reported that Gen-27, a newly synthesized flavonoid, exhibits anticancer effects against human colorectal cancer cells. In this study, we investigated the anticancer effects in human breast cancer cell lines and its underlying mechanisms. We demonstrated that Gen-27 inhibited the growth and prolifer...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.11.001
更新日期:2017-02-01 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::MRP1 overexpression in multidrug-resistant cancer cells has been shown to be responsible for collateral sensitivity to some flavonoids that stimulate a huge MRP1-mediated GSH efflux. This massive GSH depletion triggers the death of these cancer cells. We describe here that bivalent flavonoid dimers strikingly stimulat...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2016.10.013
更新日期:2017-01-15 00:00:00
abstract::The effects of 2,5-hexanedione (2,5 HD) on skeletal proteins of red blood cells (RBCs) were investigated both in vitro (human RBCs) and in vivo in male Sprague-Dawley rats which had been treated with the drug for several days. We found that 2,5 HD induced the following major changes in the electrophoretic pattern of t...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90557-1
更新日期:1989-08-15 00:00:00
abstract::Aldehydes generated during radical-induced lipid peroxidation, in particular 4-hydroxynonenal, are known to inhibit growth of certain cells. To extend our arguments that free radicals might be involved in the host response against malaria parasites we tested 26 carbonyls (n-alkanals, C6-C11; 2-alkenals, C3-C9; 2,4-alk...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(87)90364-9
更新日期:1987-02-15 00:00:00
abstract::Vectorial secretion of cationic compounds across tubular epithelial cells is an important function of the kidney. This uni-directed transport is mediated by two cooperative functions, which are membrane potential-dependent organic cation transporters at the basolateral membranes and H+/organic cation antiporters at th...
journal_title:Biochemical pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.bcp.2007.12.008
更新日期:2008-05-01 00:00:00
abstract::Deoxyelephantopin (ESD) was reported to potentiate apoptosis, inhibit invasion and abolish osteoclastogenesis but no target protein was disclosed. Here, we discovered that ESD could significantly inhibit the proliferation of different cancer cells and induce apoptosis and cell cycle arrest at G(2)/M phase in HeLa cell...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2007.11.021
更新日期:2008-03-15 00:00:00
abstract::A 1.57kb BamH1 fragment containing a full-length human debrisoquine 4-hydroxylase cytochrome P450 (CYP2D6) cDNA was inserted into the BglII site of the yeast expression plasmid pMA91 and the resulting recombinant plasmid, PELT1, introduced into Saccharomyces cerevisiae strain AH22. Microsomes prepared from AH22/pELT1 ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(92)90394-x
更新日期:1992-08-18 00:00:00
abstract::The metabolism of mitozantrone, a chemotherapeutic agent used in the treatment of breast cancer, has been studied in vitro using rat liver subcellular fractions. This compound would appear to be metabolized by two interesting pathways. One involves conjugation with glucuronic acid, catalyzed most effectively by a 3-me...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(86)90127-9
更新日期:1986-05-01 00:00:00
abstract::Inhibitory effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), cannabidiol (CBD), and cannabinol (CBN), the three major constituents in marijuana, on catalytic activities of human cytochrome P450 (CYP) 1 enzymes were investigated. These cannabinoids inhibited 7-ethoxyresorufin O-deethylase activity of recombinant...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2010.01.028
更新日期:2010-06-01 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
abstract::The aim of this work is the in vitro and ex vivo assessment of the leishmanicidal activity of camptothecin and three analogues used in cancer therapy: topotecan (Hycantim®), gimatecan (ST1481) and the pro-drug irinotecan (Camptosar®) as well as its active metabolite SN-38 against Leishmania infantum. The activity of c...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2013.02.024
更新日期:2013-05-15 00:00:00
abstract::Using a continuous perfusion system, synaptosomes prepared from rat brain released [3H]norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10(-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10(-5) M), a...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(89)90460-7
更新日期:1989-07-15 00:00:00
abstract::Administration to hamsters of a highly purified human leukocyte interferon subtype, IFN-alpha A, obtained by recombinant DNA methods, abolished the efficacy of high doses of cyclophosphamide (2.5 mg/hamster) against the TBD 932 lymphosarcoma. The effect was more pronounced with concomitant than with sequential treatme...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90117-5
更新日期:1984-11-01 00:00:00
abstract::Chemical compounds derived from plants have been used since the origin of human beings to counteract a number of diseases. Among them, the natural isoquinoline alkaloid berberine has been employed in Ayurvedic and Chinese Medicine for hundreds of years with a wide range of pharmacological and biochemical effects. More...
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
abstract::Chronic oral phenobarbital treatment (50 mg/kg every 12 hr for 8 weeks), which was nontoxic and continuously protective against seizures in rats, significantly decreased folate concentration in liver (29%) but not in brain or plasma. The apparent activity of 5,10-methylenetetrahydrofolate reductase (MTR) in liver decr...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(84)90120-5
更新日期:1984-11-01 00:00:00
abstract::Bufuralol hydroxylation activities of liver microsomal cytochrome P450 (P450) enzymes were studied in the rat; the reaction has been used widely in determining levels of liver microsomal P450 2D6, which shows debrisoquine-type genetic polymorphism in humans. Liver microsomes catalyzed the conversion of bufuralol to 1'...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/0006-2952(94)90069-8
更新日期:1994-06-01 00:00:00
abstract::High concentrations of non steroidal antiinflammatory drugs (NSAIDs) exert preventive effects against carcinogenesis. Their molecular mechanism of action remains to be elucidated. Based on previous reports with salicylate, we have made the hypothesis that various NSAIDs can activate the mitogen-activated protein kinas...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/s0006-2952(01)00826-7
更新日期:2002-01-15 00:00:00
abstract::This article has been retracted consistent with Elsevier Policy on Article Withdrawal. Please see . The Publisher apologises for any inconvenience this may cause. ...
journal_title:Biochemical pharmacology
pub_type: 杂志文章
doi:10.1016/j.bcp.2006.03.026
更新日期:2006-04-18 00:00:00