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
Sq. Alam et al., 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, Journal of Molecular and Cellular Cardiology, 27(8), 1995, pp. 1593-1604
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.