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@ARTICLE{Gruteser:909072,
      author       = {Gruteser, Nadine and Baumann, Arnd},
      title        = {{E}xamination of {I}ntracellular {GPCR}-{M}ediated
                      {S}ignaling with {H}igh {T}emporal {R}esolution},
      journal      = {International journal of molecular sciences},
      volume       = {23},
      number       = {15},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {FZJ-2022-02990},
      pages        = {8516 -},
      year         = {2022},
      note         = {Personal costs (N.G.) and consumables of the study were
                      partly funded by the German Federal Ministry of Education
                      and Research (BMBF) within the project Molecular Interaction
                      Engineering, FKZ 031A095A (awarded to A.B.). Publication
                      costs were funded by the Deutsche Forschungsgemeinschaft
                      (DFG, German Research Foundation)},
      abstract     = {The GTP-binding protein-coupled receptors (GPCRs) play
                      important roles in physiology and neuronal signaling. More
                      than a thousand genes, excluding the olfactory receptors,
                      have been identified that encode these integral membrane
                      proteins. Their pharmacological and functional properties
                      make them fascinating targets for drug development, since
                      various disease states can be treated and overcome by
                      pharmacologically addressing these receptors and/or their
                      downstream interacting partners. The activation of the GPCRs
                      typically causes transient changes in the intracellular
                      second messenger concentrations as well as in membrane
                      conductance. In contrast to ion channel-mediated electrical
                      signaling which results in spontaneous cellular responses,
                      the GPCR-mediated metabotropic signals operate at a
                      different time scale. Here we have studied the kinetics of
                      two common GPCR-induced signaling pathways: (a) Ca2+ release
                      from intracellular stores and (b) cyclic adenosine
                      monophosphate (cAMP) production. The latter was monitored
                      via the activation of cyclic nucleotide-gated (CNG) ion
                      channels causing Ca2+ influx into the cell. Genetically
                      modified and stably transfected cell lines were established
                      and used in stopped-flow experiments to uncover the
                      individual steps of the reaction cascades. Using two
                      homologous biogenic amine receptors, either coupling to Go/q
                      or Gs proteins, allowed us to determine the time between
                      receptor activation and signal output. With ~350 ms, the
                      release of Ca2+ from intracellular stores was much faster
                      than cAMP-mediated Ca2+ entry through CNG channels (~6 s).
                      The measurements with caged compounds suggest that this
                      difference is due to turnover numbers of the GPCR downstream
                      effectors rather than the different reaction cascades, per
                      se},
      cin          = {IBI-1},
      ddc          = {540},
      cid          = {I:(DE-Juel1)IBI-1-20200312},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {35955656},
      UT           = {WOS:000839069100001},
      doi          = {10.3390/ijms23158516},
      url          = {https://juser.fz-juelich.de/record/909072},
}