PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 7403655

Decrease in heart contractility produced by ouabain in fibers exposed to theophylline.

W C De Mello·M Gonzalez-Castillo
View original source ↗Export metadata ↓

Abstract

The influence of theophylline on the inotrophic action of ouabain was investigated in strips of mammalian cardiac muscle. It was found that ouabain (2 X 10(-6) M) when added to preparations previously exposed to theophylline (4 mM) reduced the peak tension by 56%, the rate of tension development (dF/dt)max by 44% and the rate of twitch relaxation (dR/dt) by 65%. The possible mechanisms involved on the negative inotropic action of ouabain are discussed.

Explore related subjects

Adenosine TriphosphateAnimalsCalciumDrug InteractionsGuinea PigsIn Vitro TechniquesMyocardial ContractionOuabainTheophyllineJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

W C De Mello, M Gonzalez-Castillo. 1980. Decrease in heart contractility produced by ouabain in fibers exposed to theophylline.. https://pubmed.ncbi.nlm.nih.gov/7403655/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

The human mitochondrial genome contains a second light strand promoter.

The human mitochondrial genome must be replicated and expressed in a timely manner to maintain energy metabolism and supply cells with adequate levels of adenosine triphosphate. Central to this process is the idea that replication primers and gene products both arise via transcription from a single light strand promoter (LSP) such that primer formation can influence gene expression, with no consensus as to how this is regulated. Here, we report the discovery of a second light strand promoter (LSP2) in humans, with features characteristic of a bona fide mitochondrial promoter. We propose that the position of LSP2 on the mitochondrial genome allows replication and gene expression to be orchestrated from two distinct sites, which expands our long-held understanding of mitochondrial gene expression in humans.

Adenosine Triphosphate↗
PubMed2021

GCN2 kinase activation by ATP-competitive kinase inhibitors.

Small-molecule kinase inhibitors represent a major group of cancer therapeutics, but tumor responses are often incomplete. To identify pathways that modulate kinase inhibitor response, we conducted a genome-wide knockout (KO) screen in glioblastoma cells treated with the pan-ErbB inhibitor neratinib. Loss of general control nonderepressible 2 (GCN2) kinase rendered cells resistant to neratinib, whereas depletion of the GADD34 phosphatase increased neratinib sensitivity. Loss of GCN2 conferred neratinib resistance by preventing binding and activation of GCN2 by neratinib. Several other Food and Drug Administration (FDA)-approved inhibitors, such erlotinib and sunitinib, also bound and activated GCN2. Our results highlight the utility of genome-wide functional screens to uncover novel mechanisms of drug action and document the role of the integrated stress response (ISR) in modulating the response to inhibitors of oncogenic kinases.

Adenosine Triphosphate↗
PubMed1996

Phosphorylation and regulation of CTP synthetase from Saccharomyces cerevisiae by protein kinase A.

The phosphorylation and regulation of the URA7-encoded CTP synthetase (EC 6.3.4.2, UTP:ammonia ligase (ADP-forming)) from Saccharomyces cerevisiae by cAMP-dependent protein kinase (protein kinase A) were examined. Protein kinase A is the principal mediator of signals transmitted through the RAS/cAMP pathway in S. cerevisiae. The results of labeling experiments indicated that the phosphorylation of CTP synthetase was mediated by the RAS/cAMP pathway in vivo. In vitro, protein kinase A phosphorylated CTP synthetase at a serine residue with a stoichiometry consistent with one phosphorylation site per CTP synthetase subunit. Protein kinase A activity was dose- and time-dependent using CTP synthetase as a substrate. The dependence of protein kinase A activity on CTP synthetase was cooperative (n = 1.8) and the Km value for CTP synthetase was 73 nM. Phosphorylation of CTP synthetase with protein kinase A resulted in the stimulation (190%) of activity. The mechanism of this stimulation included an increase in the Vmax of the reaction with respect to UTP and ATP, a decrease in the Km for ATP, and a decrease in the cooperative kinetic behavior of the enzyme. Phosphorylated CTP synthetase was less sensitive to product inhibition by CTP. Protein kinase C also phosphorylates and activates CTP synthetase. Phosphorylation of CTP synthetase with protein kinases A and C together resulted in an increase in CTP synthetase activity that was slightly greater than that obtained when the enzyme was phosphorylated with either protein kinase alone.

Adenosine Triphosphate↗