THE GTP-BINDING REGULATORY PROTEINS, GS AND GI, ARE ALTERED IN ERYTHROCYTE-MEMBRANES OF PATIENTS WITH ISCHEMIC-HEART-DISEASE RESULTING FROMCORONARY ATHEROSCLEROSIS

Acute ischemic heart disease is associated with alterations in the car diac adenylate cyclase system response, although the specificity and m echanism of these events are unknown. We studied the characteristics o f inhibitory (G(i)) and stimulatory (G(s)) GTP-binding regulatory prot eins (G proteins) of adenylate cyclase in erythrocyte membranes of pat ients (n=16) with nonacute ischemic heart disease resulting from coron ary atherosclerosis. G(s) was measured by reconstitution with the reso lved catalytic unit of adenylate cyclase and by cholera toxin-catalyze d ADP-ribosylation of a 42-kD protein; G(i) was tested as a 41-kD subs trate of pertussis toxin-catalyzed ADP-ribosylation. G(s) activity was decreased by 27 +/- 2% in the cholate extract and by 25 +/- 3% in the supernatant of guanosine 5'-(gamma-thio)triphosphate-treated membrane s. The amount of cholera toxin substrate was decreased by 33 +/- 3%, a nd the pertussis toxin substrate was increased by 27 +/- 5% compared w ith healthy subjects (n=10). All changes in G-protein characteristics appear to be specific relative to other erythrocyte membrane proteins and hemoglobin. Those patients who have a decreased G(s) possess appro ximately normal G(i), and those with increased G(i) showed no change i n G(s). Patients with increased G(i) (normal G(s)) exhibited more seve re deterioration of their coronary arteries than did patients with dec reased G(s) (normal G(i)) (P<.05), but these two groups did not differ significantly in serum lipids, hormones, drug therapy, historical dat a, or baseline assessment (P<0.05).