Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium.
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.
Knapp
J
J
Institut für Pharmakologie und Toxikologie, Westfälische Wilhelms-Universität Münster, Germany. jknapp@uni-muenster.de
Bokník
P
P
Linck
B
B
Läer
S
S
Müller
F U
FU
Neumann
J
J
Vahlensieck
U
U
Schlüter
H
H
Zidek
W
W
Schmitz
W
W
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
D015226:Dinucleoside Phosphates; C020733:diadenosine tetraphosphate; D015544:Inositol 1,4,5-Trisphosphate