The effect of calcium antagonists on the activities of lipid metabolizing enzymes in the isolated ischaemically perfused and reperfused rat heart.
Isolated rat hearts were perfused with various external Ca2+ concentrations and with various Ca2+ uptake antagonists. Compared to control activities (at 1.2 mM Ca2+), 0.6 mM Ca2+ and Ca2+ antagonists inhibited triglyceride lipase (TGL) and stimulated glycerol 3-phosphate acyltransferase (GPAT). Raising external Ca2+ concentration above the control value had no effect on TGL activity but GPAT activity was greatly reduced. Therefore, it appears that GPAT, but not TGL, will respond to increases in [Ca2+]. During ischaemia the activity of TGL is increased and that of GPAT is inhibited by beta-adrenergic activation. On reperfusion, TGL activity returns to pre-ischaemic values but GPAT activity is further reduced. In this study pre-perfusion of hearts with the Ca2+ antagonist diltiazem (10(-6) M) produced the following effects on enzyme activity during ischaemia and reperfusion: after 10 min ischaemia, TGL activity was increased and GPAT activity decreased to the same extent as seen during ischaemia in control hearts; however, on reperfusion of diltiazem-perfused hearts, the activities of both TGL and GPAT returned to pre-ischaemic values. These results suggest that Ca2+ entry on reperfusion is responsible for the reperfusion-induced decrease in GPAT activity.
Griffiths
E J
EJ
Department of Biochemistry, University of Bath, UK.
Brunt
R V
RV
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008049:Lipase / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D000217:Acyltransferases; D005992:Glycerol-3-Phosphate O-Acyltransferase; D008049:Lipase; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium