Effect of essential fatty acid deficiency on forskolin binding sites, adenylate cyclase and cyclic AMP-dependent protein kinase activity, the levels of G proteins and ventricular function in rat heart.
Three groups of rats were fed semi-purified diets. Diet I was deficient in essential fatty acids (EFAD), diet II was marginally deficient in essential fatty acids (MEFAD), and diet III contained adequate levels of essential fatty acids (control). After 9 weeks, some rats within each group were killed and cardiac membranes were prepared. Adenylate cyclase activity, [3H]forskolin binding sites, the levels of G proteins (Gi and Gs) and fatty acid composition of the membrane phospholipids were measured. Typical changes of EFA deficiency were observed in fatty acid composition of the membrane phospholipids. Adenylate cyclase activity was significantly lower in membranes of EFA-deficient rats than those of the controls. The MEFAD group gave intermediate values. Similar results were obtained with forskolin-stimulated activity with different concentrations of forskolin. Concentrations of the forskolin binding sites were also lower in the EFAD, but not in the MEFAD rats compared with the controls. There was no significant difference in forskolin binding affinities among the three groups. The decrease in adenylate cyclase activity in EFA-deficient rat heart was partially restored by feeding the control diet for 5 weeks to the EFAD or the MEFAD rats. The levels of Gi alpha and Gs alpha were not significantly different in cardiac membranes of rats fed the EFAD or the MEFAD diets from those of the control group. Lower adenylate cyclase activity in hearts of EFAD rats was also reflected in correspondingly lower activity of cAMP-dependent protein kinase. The results suggest an impairment of the cellular signalling pathway for the production of cAMP in rat heart during EFA deficiency. The beta-adrenergic response of isolated heart preparations obtained from rats fed the three diets was, however, not significantly altered.
Alam
S Q
SQ
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70119, USA.
Mannino
S J
SJ
Alam
B S
BS
McDonough
K
K
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005576:Colforsin / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005228:Fatty Acids, Essential / Q000172:deficiency*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012016:Reference Values; D015398:Signal Transduction; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D005228:Fatty Acids, Essential; D008563:Membrane Lipids; D010743:Phospholipids; D011956:Receptors, Cell Surface; C085974:forskolin receptor; D005576:Colforsin; D002784:Cholesterol; D017868:Cyclic AMP-Dependent Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol