Mechanisms of the contractile effects of flosequinoxan.
In guinea-pig papillary muscles the positive inotropic effect of flosequinoxan (BTS) starting at 100 mumol/l amounted to 287.6 +/- 34.2% at 300 mumol/l without any effects on time to peak tension (103.9 +/- 2%) and relaxation time (107.1 +/- 6.7% of predrug value, respectively). 10 mumol/l carbachol attenuated the positive inotropic effect of 300 mumol/l to 166.5 +/- 11.6% (n = 10). The phosphorylation state of the inhibitory subunit of troponin (TnI) and phospholamban (PLB) in [32P]-labeled guinea-pig ventricular myocytes was increased starting at 100 mumol/l amounting to 142.5 +/- 12.6% and 130.9 +/- 2.2% at 300 mumol/l, respectively (n = 5). Furthermore, BTS (300 mumol/l) decreased phosphorylase phosphatase activity by 23.1%. It is concluded that the contractile effects of BTS are accompanied by enhanced phosphorylation of regulatory proteins which could in part be due to inhibition of phosphorylase phosphatase activity.
Zimmermann
N
N
Abteilung Allgemeine Pharmakologie, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Bodor
G S
GS
Boknik
P
P
Gams
E
E
Jones
L R
LR
Neumann
J
J
Scholz
H
H
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D010210:Papillary Muscles / Q000187:drug effects / Q000201:enzymology; D010765:Phosphorylase Phosphatase / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014336:Troponin / Q000378:metabolism; D000099211:Phospholamban
D000251:Adenosine Triphosphatases; D002135:Calcium-Binding Proteins; D002217:Carbachol; D000242:Cyclic AMP; D009124:Muscle Proteins; D010765:Phosphorylase Phosphatase; D015363:Quinolones; D014336:Troponin; D000099211:Phospholamban; C047317:flosequinoxan