FK506 does not affect cardiac contractility and adrenergic response in vitro.
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FK506 does not affect cardiac contractility and adrenergic response in vitro. / Milting, H; Janssen, P M; Wangemann, T; Kögler, H; Domeier, E; Seidler, T; Hakim, K; Grapow, M; Zeitz, Oliver; Prestle, J; Zerkowski, H R.
in: EUR J PHARMACOL, Jahrgang 430, Nr. 2-3, 2-3, 2001, S. 299-304.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - FK506 does not affect cardiac contractility and adrenergic response in vitro.
AU - Milting, H
AU - Janssen, P M
AU - Wangemann, T
AU - Kögler, H
AU - Domeier, E
AU - Seidler, T
AU - Hakim, K
AU - Grapow, M
AU - Zeitz, Oliver
AU - Prestle, J
AU - Zerkowski, H R
PY - 2001
Y1 - 2001
N2 - FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.
AB - FK506 (tacrolimus) is a new immunosuppressant being used in cardiac allograft transplantation. While cyclosporine A has been shown to exert an acute negative inotropic effect on isolated heart muscle preparations, little is known of the inotropic influence of FK506. The Ca(2+) release channel of human skeletal muscle and cardiac muscle is associated with FK506 binding proteins (FKBP), FKBP12 and FKBP12.6, respectively. FKBPs can be dissociated by treatment with FK506. As a consequence of FK506 exposure, isolated skeletal muscle and cardiac muscle ryanodine receptors show altered gating characteristics. Therefore, we analyzed the direct inotropic effect of FK506 exposure to isolated, intact heart muscle preparations from the human and rabbits. Experiments were performed on isolated, electrically stimulated right atrial auricular muscle strips obtained from human myocardium during elective open heart surgery and on intact right ventricular trabeculae from rabbit hearts. The human preparations were exposed to concentrations of 8 x 10(-9), 8 x 10(-8) and 8 x 10(-6) M FK506 followed by a cumulative dose-response curve with isoprenaline as a non-selective beta-adrenoceptor agonist. Our data suggest that FK506 does not exert any positive or negative inotropic effect in either human or rabbit myocardium.
M3 - SCORING: Zeitschriftenaufsatz
VL - 430
SP - 299
EP - 304
JO - EUR J PHARMACOL
JF - EUR J PHARMACOL
SN - 0014-2999
IS - 2-3
M1 - 2-3
ER -
