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 assembly in vitro [Fed. Proc. 39:26-29 (1980); Mol. Pharmacol. 24:493-499 (1983)], we have found that stypoldione does not accumulate sea urchin embryos in mitosis and hence does not act like a mitotic spindle poison. We have also shown this marine natural product to inhibit both amino acid and nucleoside uptake. By preloading sea urchin embryos with nucleoside (i.e., [3H]thymidine) in order to dissociate effects on uptake from those on incorporation, we found that stypoldione in fact produces no significant inhibition of the M phase-independent S1 period of DNA synthesis, a result which suggests that stypoldione has no direct effect on DNA synthesis. In contrast, stypoldione did reduce the extent of amino acid incorporation in embryos preloaded with [3H]leucine. An inhibition of incorporation was apparent as early as 20 min after fertilization, and incorporation was reduced to 50% of control by 40 min postfertilization. This result suggests that stypoldione might inhibit cleavage via an inhibition of translation, although the existence of other inhibitory mechanisms cannot yet be ruled out. Cytological examination revealed that sea urchin embryos did not progress beyond-interphase or very early prophase when incubated in the presence of 1.0 X 10(-5) M stypoldione. The nuclear membranes remained intact, and chromatin did not condense into chromosomes in these arrested embryos. These results indicate that embryos exposed to stypoldione early in the cell cycle initiate and complete the M phase-independent S1 period of DNA synthesis, but stop cell cycle progression prior to the start of prophase of mitosis. The period between S phase and mitosis is referred to, by definition, as the "G2" phase of the cell cycle. The result therefore suggest that stypoldione blocks cell cycle progression (and, ultimately, cell division) by inhibiting progression through G2. This compound may represent a new class of G2-accumulating agents.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
White SJ,Jacobs RSsubject
Has Abstractpub_date
1983-11-01 00:00:00pages
500-8issue
3eissn
0026-895Xissn
1521-0111journal_volume
24pub_type
杂志文章abstract::An opioid-like receptor has been cloned by several groups of researchers and recently shown to be activated by an endogenous heptadecapeptide termed orphanin FQ (or nociceptin). We isolated the corresponding mouse cDNA and coexpressed it in Xenopus laevis oocytes with the potassium channel subunits Kir3.1 (GIRK1) and ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), beta-naphthoflavone (beta NF), and phenobarbital (PB) cause marked induction of cytochrome P-450 (P-450)-mediated arachidonic acid metabolism in chick embryo liver. We show here that the P-450 arachidonic acid epoxygenases induced by TCDD and beta NF are immunochemically ind...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-12-01 00:00:00
abstract::Ligands that selectively inhibit human α3β2 and α6β2 nicotinic acetylcholine receptor (nAChRs) and not the closely related α3β4 and α6β4 subtypes are lacking. Current α-conotoxins (α-Ctxs) that discriminate among these nAChR subtypes in rat fail to discriminate among the human receptor homologs. In this study, we desc...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.115.100982
更新日期:2015-11-01 00:00:00
abstract::The anti-arrhythmic quinidine has been reported to be a competitive inhibitor of the catalytic activities of human liver P-450DB, including sparteine delta 2-oxidation and bufuralol 1'-hydroxylation, and we confirmed the observation that submicromolar concentrations are strongly inhibitory. Human liver microsomes oxid...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::Kinetics of the interactions between the neuromuscular blocker alcuronium, the specific muscarinic antagonist N-[methyl-3H] methyl scopolamine ([3H]NMS), and muscarinic receptors were investigated in homogenates of rat heart atria. Two effects of alcuronium on the binding of [3H]NMS could be distinguished. (a) Alcuron...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::A method was developed to measure the formation of glutathione adducts of 1-chloro-2,4-dinitrobenzene (CDNB) and 2,4-dichloro-1-nitrobenzene (DCNB) in periportal and pericentral regions of the liver lobule in the isolated perfused rat liver by surface reflectance spectrophotometry. Conjugates of DCNB and CDNB are rele...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract::Metabolism of [3H]-(+/-)-trans-1,2-dihydroxy-1,2-dihydrobenz[a] anthracene by liver microsomes isolated from control, phenobarbital-treated, and 3-methylcholanthrene-treated Long-Evans rats and from 3-methylcholanthrene-treated Sprague-Dawley rats was examined. Liver microsomes from both control and phenobarbital-trea...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
abstract::Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.65.3.623
更新日期:2004-03-01 00:00:00
abstract::Effects of ethanol on the function of Ca(2+)-activated Cl- channels activated by G protein-coupled serotonin (5-hydroxytryptamine, (5-HT)1c) and muscarinic M1 cholinergic receptors were studied in Xenopus oocytes expressing mouse whole-brain mRNA. Ethanol (25-200 mM) inhibited currents evoked by both 5-HT and acetylch...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::The levels of hepatic mRNAs for several enzymes involved in drug metabolism were measured following administration to rats of either phenobarbitone or 2-allyl-2-isopropylacetamide. There was a substantial elevation in the mRNA levels for cytochromes P450 IIB1, IIB2, and IIIA1, epoxide hydrolase, glutathione-S-transfer...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::In the rat isolated optic nerve, nitric oxide (NO) activates soluble guanylyl cyclase (sGC), resulting in a selective accumulation of cGMP in the axons. The axons are also selectively vulnerable to NO toxicity. The experiments initially aimed to determine any causative link between these two effects. It was shown, usi...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.61.1.97
更新日期:2002-01-01 00:00:00
abstract::In standard 3H-opioid binding assays, the benzoylhydrazone derivative of naloxone (6-desoxy-6-benzoylhydrazido-N-allyl-14-hydroxydihydronormorphi none; NalBzoH) inhibited mu, kappa, and delta binding at nanomolar concentrations. At concentrations as low as 1 nM, it also produced a wash-resistant inhibition of opioid b...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Potassium channels play fundamental roles in physiology. Chemically diverse drugs bind in the pore region of K+ channels. Here, we homology-modeled voltage- and Ca2+-gated K+ channel BK and voltage-gated Kv1.3 using the X-ray structures of MthK and Kv1.2, respectively, and simulated the binding of d-tubocurarine in th...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.105.017970
更新日期:2006-04-01 00:00:00
abstract::Polyamides are a class of synthetic molecules that exhibit high-affinity, sequence-specific reversible binding in the DNA minor groove but are incapable of inducing DNA damage. In cell-free systems, polyamides have been shown to regulate gene expression by activation, repression, and antirepression. However, effective...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.104.006254
更新日期:2005-03-01 00:00:00
abstract::Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and no...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-06-01 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::5-Hydroxytryptamine3 (5-HT3) receptors are ligand-gated ion channels that mediate neurotransmission by serotonin in the central nervous system. Pharmacological inhibition of 5-HT3 receptor activity has therapeutic potential in several psychiatric diseases, including depression and anxiety. The recently approved multim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.118.113530
更新日期:2018-12-01 00:00:00
abstract::Phosphorylation of tau protein promotes stability of the axonal cytoskeleton; aberrant tau phosphorylation is implicated in the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases and phosphatases that modulate tau phosphorylation have been identified using in vitro techniques; ho...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1999-04-01 00:00:00
abstract::We have, in the accompanying work, demonstrated the coexistence of M2 and M3 muscarinic receptors in the circular smooth muscle of canine colon. In the present study, the effects of muscarinic receptor stimulation on phosphoinositide turnover and adenylate cyclase activity were examined. In myo-[3H]inositol-labeled ci...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::Pyrethroid insecticides are synthetic neurotoxins patterned after the naturally occurring pyrethrins. Their mechanism of action is thought to involve effects primarily at the voltage-sensitive sodium channel of both insect and mammalian neurons, although recent studies have raised the possibility that these compounds ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Macrophage production of growth factors for fibroblasts, in particular platelet-derived growth factor B [PDGF(B)] and transforming growth factor-beta (TGF-beta), is thought to be central to the pathogenesis of pulmonary fibrosis. In a search for anti-inflammatory agents that might prevent this process, we asked whethe...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::4-PIOL is a structural analog of GABA that has low efficacy at GABAA receptor CI- channels and activates a nondesensitizing CI- conductance in central neurons. We investigated the biophysical mechanisms of its low efficacy in embryonic olfactory bulb neurons, which express a limited number of GABAA receptor subunit tr...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::The nonselective cation channel TRPA1 (ANKTM1, p120) is a potential mediator of pain, and selective pharmacological modulation of this channel may be analgesic. Although several TRPA1 activators exist, these tend to be either reactive or of low potency and/or selectivity. The aim of the present study, therefore, was t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.107.042663
更新日期:2008-04-01 00:00:00
abstract::Five separate guanine nucleotide-binding proteins (G proteins) were immunologically identified in membranes from neuroblastoma x glioma NG108-15 hybrid cells. These alpha subunit proteins were Gi2 alpha, two isoforms of Gi3 alpha, and two isoforms of Go alpha. The G proteins that interacted with delta-opioid receptors...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) suppresses many immune responses, both innate and adaptive. Suppression is mediated by the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor. The AhR mediates TCDD toxicity presumably through the alteration of transcriptional events, either by promoting...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.62.3.722
更新日期:2002-09-01 00:00:00
abstract::Adult guinea pig hippocampal membranes contain two 5-hydroxytryptamine (5-HT) receptors positively coupled with an adenylate cyclase. One is a typical 5-HT1A receptor and the second is a nonclassical 5-HT receptor that we previously proposed to call 5-HT4. Here, we show that 4-amino-5-chlor-2-methoxy-benzamide derivat...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::ATP-gated purinergic receptors (P2XRs) are a family of cation-permeable channels that conduct Ca(2+) and facilitate voltage-sensitive Ca(2+) entry in excitable cells. To study Ca(2+) signaling by P2XRs and its dependence on voltage-sensitive Ca(2+) influx, we expressed eight cloned P2XR subtypes individually in gonado...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.58.5.936
更新日期:2000-11-01 00:00:00
abstract::The X-ray and NMR structural study of 3-carbomethoxy rifamycin S5 was undertaken in order to determine whether its low antimicrobial activity was related to a conformation of the molecule which was unfavorable for interaction with bacterial DNA-dependent RNA polymerase. However, the molecule assumes a conformation sim...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the ...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:10.1124/mol.116.107623
更新日期:2017-04-01 00:00:00
abstract::The 2,3,7,8-tetrachlorodibenzo-p-dioxin-transformed aryl hydrocarbon receptor (AHR) complex binds to xenobiotic-responsive element (XRE) sequences in the 5' flanking region of the CYP1A1 gene, resulting in initiation of transcription. Both components of the transformed AHR complex [the ligand-binding AHR monomer and t...
journal_title:Molecular pharmacology
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00