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W Rouslin

Publications and source records attributed to W Rouslin.

47 records · Page 3Linked to original sources
PubMed1980

Effects of RMI 12330A, a new inhibitor of adenylate cyclase on myocardial function and subcellular activity.

1 RMI 12330A, a lactam-imine, at concentrations of 10(-4) M and higher, inhibited basal as well as isoprenaline and NaF-stimulated adenylate cyclase activity of guinea-pig heart homogenates. However, RMI 12330A was a more potent inhibitor of histamine-stimulated adenylate cyclase (IC50 of 1.5 X 10(-5) M). 2 In the isolated work-performing heart of the guinea-pig, RMI 12330A (IC50 of 1.1 X 10(-6) M) depressed all cardiac functions: pressures developed, dP/dt, contractile force, dF/dt, work performance and stroke work. Left atrial pressure rose and the positive inotropic response to increasing heart rate (staircase) became negative. Histamine, isoprenaline and ouabain no longer caused positive inotropic effects. 3 Increasing the perfusate calcium concentration from 2.5 mM to 4.5 and 6.5 mM completely restored cardiac function after its depression by RMI 12330A. 4 RMI 12330A uncoupled mitochondrial oxidative phosphorylation; the classical uncoupler, dinitrophenol, had the same effects on cardiac dynamics as RMI 12330A. 5 RMI in high doses inhibited hydrolytic activity of Na+, K+-ATPase of crude and purified heart preparations (IC50 of 1.7 X 10(-4) M) and inhibited ouabain binding to the same enzymes (IC50 of 1.5 X 10(-4) M). 6 A lactam-imine analogue of RMI 12330A that had no effect on adenylate cyclase, was also without effect on any of the systems examined.

Adenylyl Cyclase Inhibitors↗
PubMed1979

Effects of cerulenin upon the syntheses of lipid and protein and upon the formation of respiratory enzymes in adapting, lipid-limited Saccharomyces cerevisiae.

When bakers' yeast cells were grown anaerobically in a medium supplemented with Tween 80 and ergosterol, exposure during aeration to the fatty acid synthesis inhibitor, cerulenin, had little effect upon respiratory adaptation, the induction of enzymes of electron transport, or the in vivo incorporation of [(14)C]leucine into mitochondrial membranes. These lipid-supplemented cells were apparently able to undergo normal respiratory adaptation utilizing endogenous lipids alone. The level of cerulenin used (2 mug/ml) inhibited the in vivo incorporation of [(14)C]acetate into mitochondrial membrane lipids by 96%. If, however, the cells were deprived of exogenous lipid during anaerobic growth, subsequent exposure to cerulenin severely reduced their capacity to undergo respiratory adaptation, to form enzymes of electron transport, and to incorporate amino acid into both total cell and mitochondrial membrane proteins. This cerulenin-mediated inhibition of enzyme formation and of protein synthesis was nearly completely reversed by the addition of exogenous lipid during the aeration of the cells. In lipid-limited cells, chloramphenicol also had dramatic inhibitory effects, both alone (75%) and together with cerulenin (85%), upon total cell and mitochondrial membrane [(14)C]leucine incorporation. This marked chloramphenicol-mediated inhibition was also largely reversed by exogenous lipid. It is concluded that, in lipid-limited cells, either cerulenin or chloramphenicol may prevent the emergence of a pattern of lipids required for normal levels of protein synthetic activity. The effect of cerulenin upon the formation of mitochondrial inner membrane enzymes thus appears to reflect a nonspecific effect of this antilipogenic antibiotic upon total cell protein synthesis.

Antifungal Agents↗