Effect of platelet-activating factor (PAF) on sodium calcium exchange in cardiac sarcolemmal vesicles.
The effects of platelet-activating factor (PAF) on Na(+)-dependent calcium uptake in myocardial sarcolemmal vesicles were examined in order to clarify its mechanism of inotropic action on the heart. PAF (40 and 20 microM) significantly inhibited Na(+)-Ca2+ exchange by 61% and 37%, respectively. Both initial rate of exchange and maximal exchange were inhibited. The Km for the reaction was not altered but Vmax was lowered 55% by PAF. Lyso-PAF inhibited Na(+)-Ca2+ exchange to a similar degree as PAF. CV-3988, a specific PAF receptor antagonist, failed to diminish the inhibitory effect of PAF on Na(+)-Ca2+ exchange, suggesting that the effect of PAF on Na(+)-Ca2+ exchange is not via a receptor mechanism. The passive permeability of sarcolemmal vesicles to Ca2+ was markedly elevated after PAF treatment. However, this effect could not account for the decrease in Na(+)-Ca2+ exchange. Interestingly, passive Ca2+ binding to cardiac sarcolemma was increased by 40 microM PAF. This study indicates that a depression of Na(+)-Ca2+ exchange probably does not play a role in the negative inotropic effect of PAF on the myocardium under physiological conditions. Its mechanism of action on Na(+)-Ca2+ exchange is discussed.
Meng
H P
HP
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Center, Winnipeg, Canada.
Kutryk
M J
MJ
Pierce
G N
GN
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000493:pharmacokinetics*; D004285:Dogs; D009206:Myocardium / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000493:pharmacokinetics*
D010972:Platelet Activating Factor; D012964:Sodium; D002118:Calcium