| Abstrakt: |
To test the general hypothesis that cardiac inneervation may participate in myocardial G protein regulation, we examined the effects of complete intrapericardial surgical denervalion or sham operation in dogs. In particulate fractions of dog left ventricular (I.V) myocardium harvested 28—33 days after denervation or sham operation. M140,000 and M139,000 pertussis toxinsensitive substrates (G proteins) were increased by 31 (1.31 ± 0.084 vs 1.0 ± 0.058 OD, arbitrary units, p 0.01) and 4 (1.40 ± 0.1 vs. 1.000 ± 0.084 OD, arbitrary units, p ≤ 0.02), respectively, as compared With sham-operated controls. The M140,000 pectussis toxinsensitive band comigrated with a pertussis toxin-sensitive substrate in human crythrocyte membranes known to contain an G1species. In these same preparations basal. GIP and GppNHp stimulated adenylate cyclase activities were decreased in denervated heart by 20, 26, and 19, respectively, consistent with increased activity of an inhibitory G protein. In contrast. G function was not altered, because cyct membranes reconstituted with membrane extracts and fluoride and β-receptor-stimulated adenylate cyclase activity were not different between groups. Furthermore, adenylate cyclase catalytic subunit function as assessed with forskolin and manganese stimulation wits not different between preparations of control and denervated heart. We conclude that in preparations of surgically denervated dog myocardium M140,000 and M139,000 pertussis toxin-sensitive G proteins are increased by 31 and 40, respectively, and that functional alterations in adenylate cyclase activity exist, consistent with increased inhibitory G-protein function. |
