The influence of mono- and divalent cations on the cardiac metabolism of arachidonic acid.
Our previous study indicated that, in the isolated rabbit heart, perfusion with Ca2+ free Krebs Henseleit buffer (KHB) results in increased conversion of exogenous arachidonic acid to PGE2 and 6-keto-PGF1 alpha, probably as the result of increased availability of substrate to cyclooxygenase. Since perfusion with Ca2+ free buffer is known to cause alterations in the cardiac content of various mono- and divalent cations, the present study was performed to determine: a) The relationship between the conversion of exogenous arachidonic acid to prostaglandins and cardiac content of Na+, K+, Ca2+ and Mg2+; and b) Whether enhanced arachidonic acid conversion to prostaglandins during Ca2+ free perfusion is due to reduced incorporation of this fatty acid into tissue lipids. Perfusion of the rabbit heart with Ca2+ free buffer produced a significant reduction in the tissue content of Na+, K+, Ca2+ and Mg2+. However, the production of 6-keto-PGF1 alpha from exogenous arachidonic acid was linearly correlated with tissue Mg2+. These observations, together with our finding that perfusion with Ca2+ free KHB reduced the incorporation of [3H] arachidonic acid into tissue lipids, suggests that Ca2+ free perfusion may, by reducing the activity of arachidonyl CoA synthetase (a Mg2+ dependent enzyme), decrease the acylation of arachidonic acid into lipids, thus increasing the availability of arachidonic acid to cyclooxygenase.
Weis
M T
MT
Dept. of Pharmacology, University of Tennessee, Memphis 38163.
Malik
K U
KU
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D002414:Cations, Monovalent / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D006339:Heart Rate; D050356:Lipid Metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000494:pharmacology; D014316:Tritium
D001095:Arachidonic Acids; D002413:Cations, Divalent; D002414:Cations, Monovalent; D010710:Phosphates; D014316:Tritium; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D012964:Sodium; D008274:Magnesium; D015232:Dinoprostone; D011188:Potassium; D002118:Calcium