title: DMACM-caged adenosine nucleotides: ultrafast phototriggers for ATP, ADP, and AMP activated by long-wavelength irradiation.
abstract: The development of new photocleavable adenosine nucleotides based on the photochemistry of [7-(dimethylamino)coumarin-4-yl]methyl (DMACM) esters is described. The phototriggers liberate adenosine triphosphate (ATP), diphosphate, and monophosphate upon UV/Vis irradiation between 334 and 405 nm. The efficiency of photocleavage at long wavelengths is high as a result of a combination of appropriate quantum yields and intensive absorptivities. By using time-resolved fluorescence spectroscopy, we determined a lower limit of 1.6 x 10(9) s(-1) for the rate constant of the release of ATP from DMACM-caged ATP. The favorable properties of DMACM-caged ATP were confirmed in physiological studies by confocal laser scanning microscopy. We were able to uncage DMACM-caged ATP in cultures of mouse astrocytes and in brain tissue slices from mice and were also able to measure the effect of photoreleased ATP on the cellular response of astrocytes, namely the ability of the ATP to evoke Ca(2+) ion waves.
authors.affiliation: Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Strasse 10, 13125 Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Geissler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kresse
authors.forename: Burkhard
authors.initials: B
authors.lastname: Wiesner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bendig
authors.forename: Helmut
authors.initials: H
authors.lastname: Kettenmann
authors.forename: Volker
authors.initials: V
authors.lastname: Hagen
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism / Q000493:pharmacokinetics*; D000249:Adenosine Monophosphate / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003374:Coumarins / Q000138:chemical synthesis*; D004952:Esters; D051379:Mice; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D003374:Coumarins; D004952:Esters; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; C092582:7-dimethylamino-4-methylcoumarin; D000255:Adenosine Triphosphate; D002118:Calcium