title: Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium.
abstract: In human ventricular trabeculae carneae 100 microM AP4A (diadenosine tetraphosphate) increased force of contraction to 162.8+/-15.7% of predrug value (n=9). This positive inotropic effect was accompanied by a prolongation of time parameters: time to peak tension and time of relaxation were prolonged by 7.8+/-1.3% and 14.9+/-3.8%, respectively (P<0.05). In the same trabeculae, AP4A increased IP3 (inositol-1,4,5-trisphosphate) content from 9.0+/-1.3 pmol/mg to 22.9+/-5.4 pmol/mg protein (n=5-9). In conclusion, the positive inotropic effect of AP4A in the human myocardium is likely due to an increase of IP3 mediated probably via Gq-coupled P2Y-purinoceptors. Because of the prominent role of Gq in the development of cardiac disease, these findings may lay the ground to further investigate the possible role of AP4A and/or related ligands (e.g. AP2A and AP3A) in heart failure.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Germany. jknapp@uni-muenster.de
authors.forename: J
authors.initials: J
authors.lastname: Knapp
authors.forename: P
authors.initials: P
authors.lastname: Bokník
authors.forename: B
authors.initials: B
authors.lastname: Linck
authors.forename: S
authors.initials: S
authors.lastname: Läer
authors.forename: F U
authors.initials: FU
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: U
authors.initials: U
authors.lastname: Vahlensieck
authors.forename: H
authors.initials: H
authors.lastname: Schlüter
authors.forename: W
authors.initials: W
authors.lastname: Zidek
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
mesh_terms: D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D013997:Time Factors
chemical_list: D015226:Dinucleoside Phosphates; C020733:diadenosine tetraphosphate; D015544:Inositol 1,4,5-Trisphosphate