Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations
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Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations. / Vahlensieck, U; Bokník, P; Gombosová, I; Huke, S; Knapp, J; Linck, B; Lüss, H; Müller, F U; Neumann, J; Deng, M C; Scheld, H H; Jankowski, H; Schlüter, H; Zidek, W; Zimmermann, N; Schmitz, W.
In: The Journal of pharmacology and experimental therapeutics, Vol. 288, No. 2, 02.1999, p. 805-13.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Inotropic effects of diadenosine tetraphosphate (AP4A) in human and animal cardiac preparations
AU - Vahlensieck, U
AU - Bokník, P
AU - Gombosová, I
AU - Huke, S
AU - Knapp, J
AU - Linck, B
AU - Lüss, H
AU - Müller, F U
AU - Neumann, J
AU - Deng, M C
AU - Scheld, H H
AU - Jankowski, H
AU - Schlüter, H
AU - Zidek, W
AU - Zimmermann, N
AU - Schmitz, W
PY - 1999/2
Y1 - 1999/2
N2 - Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.
AB - Diadenosine tetraphosphate (AP4A) is an endogenous compound and exerts diverse physiological effects in animal systems. However, the effects of AP4A on inotropy in ventricular cardiac preparations have not yet been studied. The effects of AP4A on force of contraction (FOC) were studied in isolated electrically driven guinea pig and human cardiac preparations. Furthermore, the effects of AP4A on L-type calcium current and [Ca]i were studied in isolated guinea pig ventricular myocytes. In guinea pig left atria, AP4A (0.1-100 microM) reduced FOC maximally by 36.5 +/- 4.3%. In guinea pig papillary muscles, AP4A (100 microM) alone was ineffective, but reduced isoproterenol-stimulated FOC maximally by 29.3 +/- 3.4%. The negative inotropic effects of AP4A in atria and papillary muscles were abolished by the A1-adenosine receptor antagonist 1, 3-dipropyl-cyclopentylxanthine. In guinea pig ventricular myocytes, AP4A (100 microM) attenuated isoproterenol-stimulated L-type calcium current and [Ca]i. In human atrial and ventricular preparations, AP4A (100 microM) alone increased FOC to 158.3 +/- 12.4% and 167.5 +/- 25.1%, respectively. These positive inotropic effects were abolished by the P2-purinoceptor antagonist suramin. On the other hand, AP4A (100 microM) reduced FOC by 27.2 +/- 7.4% in isoproterenol-stimulated human ventricular trabeculae. The latter effect was abolished by 1,3-dipropyl-cyclopentylxanthine. In summary, after beta adrenergic stimulation AP4A exerts negative inotropic effects in animal and human ventricular preparations via stimulation of A1-adenosine receptors. In contrast, AP4A alone can exert positive inotropic effects via P2-purinoceptors in human ventricular myocardium. Thus, P2-purinoceptor stimulation might be a new positive inotropic principle in the human myocardium.
KW - Animals
KW - Calcium
KW - Calcium Channels
KW - Cells, Cultured
KW - Dinucleoside Phosphates
KW - Drug Interactions
KW - Guinea Pigs
KW - Heart
KW - Heart Atria
KW - Heart Ventricles
KW - Humans
KW - In Vitro Techniques
KW - Male
KW - Myocardial Contraction
KW - Myocardium
KW - Platelet Aggregation Inhibitors
KW - Xanthines
KW - Comparative Study
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
M3 - SCORING: Journal article
C2 - 9918592
VL - 288
SP - 805
EP - 813
JO - J PHARMACOL EXP THER
JF - J PHARMACOL EXP THER
SN - 0022-3565
IS - 2
ER -