Cisplatinum enhancement of myocardial Mg2+ transport.
Cisplatinum in a concentration (4.3 x 10(-6) M) corresponding to the therapeutic plasma concentration for cancer patients was found to cause a marked enhancement of magnesium efflux and uptake in perfused frog myocardium. The magnesium content of the perfused frog ventricle is increased from 6.66 +/- 0.34 mumol/g wet wgt to 8.03 +/- 0.38 mu mol/g wet wgt. Cisplatinum had a negative inotropic action reducing contractile force to 46 +/- 8% of initial force after 40 min of perfusion. The corresponding control contractile force was reduced to 74 +/- 7%. Removal of calcium and magnesium from the perfusion solution containing 0.5 mM EDTA for 10 minutes caused contractile force to be reduced to 0 after 6 beats at 24 min-1. After ten minutes of perfusion with EDTA, 1.87 mu mol/g wet wgt of magnesium was lost from control ventricles. Cisplatinum increased the loss to 4.08 +/- 0.34 mu mol/g wet wgt. The magnesium lost during EDTA perfusion was completely recovered after 5 minutes of perfusion in Ringer or Tyrode solution by both control and cisplatinum treated frog ventricles. The contractile force also recovered to the level prior to perfusion with EDTA Ringer. The rate of Mg2+ efflux in EDTA Ringer is largest during the first 3 minutes and was 0.170 +/- 0.051 p mol cm-2 sec-1 for controls and 0.798 p mol cm-2 sec-1 for the cisplatinum treated ventricles. During the last 7 min of perfusion in EDTA Ringer the Mg2+ efflux was reduced to 0.057 +/- 0.005 p mol cm-2 sec-1 for control ventricles and 0.170 p mol cm-2 sec-1 for the cisplatinum treated ventricles. Cisplatinum increased both magnesium efflux and influx and influx in the frog myocardium, increased magnesium content to a higher level and reduced contractile force. The effect of cisplatinum on magnesium transport is attributed to an increase in the charged form of cisplatinum that accumulates inside the cell where chloride content is low and the chloride of cisplatinum is displaced to form a positively charged cisplatinum.
Department of Pharmacology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
L
L
Murphy
J M
JM
Procopio
C P
CP
Bianchi
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001001:Anura; D002945:Cisplatin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D017136:Ion Transport; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism
D000970:Antineoplastic Agents; D008274:Magnesium; D002945:Cisplatin