Time course of alterations in phospholipid fatty acids and number of beta-adrenoceptors in the rat heart during adrenergic stimulation in vivo.
The purpose of this study was to test the hypothesis that catecholamine induced down-regulation of beta-adrenoceptors in cardiac muscle is facilitated by modifications of the lipid milieu in cellular membranes. The time course of down-regulation of beta -adrenoceptors and changes in the fatty acid composition of phospholipids was examined in the rat heart during adaptation to repeated epinephrine administration. By this we studied a possible relationship between modulation of the membrane phospholipids and the properties of beta-adrenoceptors during 7 days of epinephrine administration. The fatty acid composition of cardiac membrane phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and Bmax and Kd of [3H]dihydroalprenolol binding to beta -adrenoceptors were measured in rats after 1, 2, 3, 5 and 7 days of epinephrine administration. The in vivo adrenergic stimulation led to a significant response of phospholipid fatty acyl chains. In both PC and PE the linoleic acid (18:2n-6) level decreased markedly. The docosahexanoic acid (22:6n-3) level increased in PE and the arachidonic acid (20:4n-6) level increased in PC. These fatty acid changes were all significant after 3-5 days of epinephrine administration. During the 7 day epinephrine administration, the polyunsaturated fatty acid levels in the phospholipids of purified cardiac sarcolemma changed in the same way as in the phospholipids of whole ventricular muscle. The number of binding sites of beta -adrenoceptors (Bmax) decreased as expected. The decrease in Bmax occurred later than the changes in their lipid environment and was only significant after 7 days of epinephrine administration. The conclusion is that during adaptation to epinephrine administration, the down-regulation of beta-adrenoceptors is preceded by alterations in the polyunsaturated fatty acid composition of phospholipids in heart muscle. This supports the concept of a regulatory role of membrane lipids in the response of beta-adrenoceptors to prolonged stimulation.
Benediktsdóttir
V E
VE
Science Institute, University of Iceland, Vatnsmýrarvegur 16, Reykjavik, IS-101, Iceland.
Curvers
J
J
Gudbjarnason
S
S
D000322:Adrenergic Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015536:Down-Regulation; D004837:Epinephrine / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D016014:Linear Models; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D000322:Adrenergic Agonists; D000318:Adrenergic beta-Agonists; D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D004837:Epinephrine