Relaxation of vascular and tracheal smooth muscle by cyclic nucleotide analogs that preferentially activate purified cGMP-dependent protein kinase.


: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 promoting relaxation of K+-induced contractions. Significant relaxation of this tissue was caused primarily by those cyclic nucleotide analogs that had high affinities for purified cG-K but not for cA-K. The low potencies of cA-K-specific analogs, as compared with cG-K-specific analogs, could not be readily explained by either unusually high susceptibilities to phosphodiesterases or low partition coefficients. The most potent cGMP analog, 8-(4-chlorophenylthio)-cGMP, exhibited a very slow reversibility of its relaxant effects in the intact tissue, consistent with its strong resistance to hydrolysis by phosphodiesterases measured in vitro. Pig coronaries contained atypically high levels of cGMP and cG-K, implying a potentially important role of this enzyme in smooth muscle function. Carbamylcholine-induced contractions of guinea pig tracheal segments were more sensitive than K+-induced pig coronary artery contractions to relaxation by cyclic nucleotide analogs. Consequently, the number of analogs that could be studied was significantly expanded. The cGMP analogs were again generally more potent, and the effectiveness of both cGMP and cAMP analogs in relaxing this preparation correlated with the Ka of the analogs for in vitro activation of cG-K, but not cA-K. A particularly strong correlation was observed when the effects of analogs modified only at the C-8 position were examined. A known target enzyme of cA-K, phosphorylase, was not activated by cG-K-specific analogs but was activated by high concentrations of the cA-K-specific analogs. Studies using cyclic nucleotide analogs support a role for cG-K, but not for cA-K, in decreasing smooth muscle tone.


Mol Pharmacol


Molecular pharmacology


Francis SH,Noblett BD,Todd BW,Wells JN,Corbin JD


Has Abstract


1988-10-01 00:00:00












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    abstract::The heart is richly endowed with K(ATP) channels, which function as biological sensors, regulating membrane potentials and electrical excitability in response to metabolic alterations. We recently reported that the cytochrome P450 metabolites of arachidonic acid, epoxyeicosatrienoic acids (EETs), potently activate car...

    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Lu T,VanRollins M,Lee HC

    更新日期:2002-11-01 00:00:00

  • CCAAT/enhancer-binding protein beta (nuclear factor for interleukin 6) transactivates the human MDR1 gene by interaction with an inverted CCAAT box in human cancer cells.

    abstract::We investigated the mechanisms of MDR1 gene activation by CCAAT/enhancer binding protein beta (C/EBPbeta, or nuclear factor for interleukin 6) in human cancer cells. Transfection of the breast cancer cell line MCF-7 and its doxorubicin-selected variant MCF-7/ADR by either C/EBPbeta or C/EBPbeta-LIP (a dominant-negativ...

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    pub_type: 杂志文章


    authors: Chen KG,Sale S,Tan T,Ermoian RP,Sikic BI

    更新日期:2004-04-01 00:00:00

  • Modulation of platelet-derived growth factor B mRNA abundance in macrophages by colchicine and dibutyryl-cAMP.

    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


    authors: Wangoo A,Haynes AR,Sutcliffe SP,Sorooshian M,Shaw RJ

    更新日期:1992-10-01 00:00:00

  • Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators.

    abstract::The compound 4-(5-(4-bromophenyl)-3-(6-methyl-2-oxo-4-phenyl-1,2-dihydroquinolin-3-yl)-4,5-dihydro-1H-pyrazol-1-yl)-4-oxobutanoic acid (DQP-1105) is a representative member of a new class of N-methyl-d-aspartate (NMDA) receptor antagonists. DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values ...

    journal_title:Molecular pharmacology

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    authors: Acker TM,Yuan H,Hansen KB,Vance KM,Ogden KK,Jensen HS,Burger PB,Mullasseril P,Snyder JP,Liotta DC,Traynelis SF

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    journal_title:Molecular pharmacology

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    authors: Narushima K,Takada T,Yamanashi Y,Suzuki H

    更新日期:2008-07-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Hejazi N,Zhou C,Oz M,Sun H,Ye JH,Zhang L

    更新日期:2006-03-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Driscoll WJ,Mueller SA,Eipper BA,Mueller GP

    更新日期:1999-06-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Hartley RM,Peng J,Fest GA,Dakshanamurthy S,Frantz DE,Brown ML,Mooberry SL

    更新日期:2012-03-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Lilienblum W,Bock-Hennig BS,Bock KW

    更新日期:1985-04-01 00:00:00

  • Inhibition of trail gene expression by cyclopentenonic prostaglandin 15-deoxy-delta12,14-prostaglandin J2 in T lymphocytes.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Fionda C,Nappi F,Piccoli M,Frati L,Santoni A,Cippitelli M

    更新日期:2007-11-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 评论,杂志文章,评审


    authors: White MM

    更新日期:2006-02-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Zhu D,Tate RI,Ruediger R,Meigs TE,Denker BM

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  • Resistance to etoposide in human leukemia HL-60 cells: reduction in drug-induced DNA cleavage associated with hypophosphorylation of topoisomerase II phosphopeptides.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Ganapathi R,Constantinou A,Kamath N,Dubyak G,Grabowski D,Krivacic K

    更新日期:1996-08-01 00:00:00

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    pub_type: 杂志文章


    authors: Galvez T,Urwyler S,Prézeau L,Mosbacher J,Joly C,Malitschek B,Heid J,Brabet I,Froestl W,Bettler B,Kaupmann K,Pin JP

    更新日期:2000-03-01 00:00:00

  • Xbal 16- plus 9-kilobase DNA restriction fragments identify a mutant allele for debrisoquin hydroxylase: report of a family study.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Evans WE,Relling MV

    更新日期:1990-05-01 00:00:00

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    abstract::Maurotoxin (MTX) is a potent blocker of human voltage-activated Kv1.2 and intermediate-conductance calcium-activated potassium channels, hIKCa1. Because its blocking affinity on both channels is similar, although the pore region of these channels show only few conserved amino acids, we aimed to characterize the bindin...

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


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    authors: Beqollari D,Betzenhauser MJ,Kammermeier PJ

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Laz TM,Forray C,Smith KE,Bard JA,Vaysse PJ,Branchek TA,Weinshank RL

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  • Differential effects of ethanol on electrical properties of various potassium channels expressed in oocytes.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Anantharam V,Bayley H,Wilson A,Treistman SN

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  • CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Busi F,Cresteil T

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  • Effects of steroids on gamma-aminobutyric acid receptors expressed in Xenopus oocytes by poly(A)+ RNA from mammalian brain and retina.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Woodward RM,Polenzani L,Miledi R

    更新日期:1992-01-01 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Flaim KE,Jefferson LS,McGwire JB,Rannels DE

    更新日期:1983-09-01 00:00:00

  • Proteomic approaches to investigate regulated trafficking and signaling of GPCRs.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: von Zastrow M

    更新日期:2020-12-22 00:00:00

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Snyders J,Knoth KM,Roberds SL,Tamkun MM

    更新日期:1992-02-01 00:00:00

  • Mss4 gene is up-regulated in rat brain after chronic treatment with antidepressant and down-regulated when rats are anhedonic.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Andriamampandry C,Muller C,Schmidt-Mutter C,Gobaille S,Spedding M,Aunis D,Maitre M

    更新日期:2002-12-01 00:00:00

  • Evidence for a second receptor for prostacyclin on human airway epithelial cells that mediates inhibition of CXCL9 and CXCL10 release.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Wilson SM,Sheddan NA,Newton R,Giembycz MA

    更新日期:2011-03-01 00:00:00

  • The tricyclic antidepressant amitriptyline inhibits D-cyclin transactivation and induces myeloma cell apoptosis by inhibiting histone deacetylases: in vitro and in silico evidence.

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    journal_title:Molecular pharmacology

    pub_type: 杂志文章


    authors: Mao X,Hou T,Cao B,Wang W,Li Z,Chen S,Fei M,Hurren R,Gronda M,Wu D,Trudel S,Schimmer AD

    更新日期:2011-04-01 00:00:00