Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium
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Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium. / Knapp, J; Bokník, P; Linck, B; Läer, S; Müller, F U; Neumann, J; Vahlensieck, U; Schlüter, H; Zidek, W; Schmitz, W.
In: N-S ARCH PHARMACOL, Vol. 360, No. 3, 09.1999, p. 354-7.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inositol-1,4,5-trisphosphate increase by diadenosine tetraphosphate in preparations from failing human myocardium
AU - Knapp, J
AU - Bokník, P
AU - Linck, B
AU - Läer, S
AU - Müller, F U
AU - Neumann, J
AU - Vahlensieck, U
AU - Schlüter, H
AU - Zidek, W
AU - Schmitz, W
PY - 1999/9
Y1 - 1999/9
N2 - 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.
AB - 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.
KW - Cardiomyopathies
KW - Dinucleoside Phosphates
KW - Electric Stimulation
KW - Heart Ventricles
KW - Humans
KW - In Vitro Techniques
KW - Inositol 1,4,5-Trisphosphate
KW - Male
KW - Middle Aged
KW - Myocardial Contraction
KW - Time Factors
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 10543439
VL - 360
SP - 354
EP - 357
JO - N-S ARCH PHARMACOL
JF - N-S ARCH PHARMACOL
SN - 0028-1298
IS - 3
ER -