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 deficien t 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 ea ch group were killed and cardiac membranes were prepared. Adenylate cy clase activity, [H-3]forskolin binding sites, the levels of G proteins (Gi and Gs) and fatty acid composition of the membrane phospholipids were measured. Typical changes of EPA deficiency were observed in fatt y acid composition of the membrane phospholipids. Adenylate cyclase ac tivity was significantly lower in membranes of EFA-deficient rats than those of the controls, The MEFAD group gave intermediate values. Simi lar results were obtained with forskolin-stimulated activity with diff erent concentrations of forskolin. Concentrations of the forskolin bin ding sites were also lower in the EFAD, but not in the MEPAD rats comp ared with the controls, There was no significant difference in forskol in binding affinities among the three groups, The decrease in adenylat e cyclase activity in EFA-deficient rat heart was partially restored b y 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 i n cardiac membranes of rats fed the EFAD or the MEFAD diets from those of the control group. Lower adenylate cyclase activity in hearts of E FAD rats was also reflected in correspondingly lower activity of cAMP- dependent protein kinase. The results suggest an impairment of the cel lular signalling pathway for the production of cAMP in rat heart durin g EFA deficiency, The beta-adrenergic response of isolated heart prepa rations obtained from rats fed the three diets was, however, not signi ficantly altered. (C) 1995 Academic Press Limited.