The effect of surface-active agents on pancreatic lipase.
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A study was made of the effects of various types of detergents on the swelling of isolated mitochondria and on mitochondrial ATPases which are activated by Mg or DNP respectively. The rate of swelling was measured in the Beckman spectrophotometer by following the decrease in turbidity of dilute suspensions of these organelles. It was found that non-ionic detergents containing a nonyl phenoxy side chain or anionic detergents caused swelling of the mitochondria and activation of Mg-ATPase. On the other hand, cationic detergents promoted the clumping of mitochondria and did not activate Mg-ATPase. DNP-ATPase was inhibited by all of the detergents tested. It would appear from these observations that the inhibition of DNP-ATPase is not related to a gross change in the morphology of the organelles; in contrast, the activation of Mg-ATPase definitely is correlated with swelling of the isolated mitochondria. These data also suggest that the ionic detergents combine with charged sites on the protein moiety of the lipoprotein in the mitochondrial surface, whereas the non-ionic detergents form inclusion compounds with the lipide moiety, thereby altering the mitochondrial structure and permeability.
Guinea pigs given three subcutaneous injections of triton WR-1339, 300 mg./kg., at 3 day intervals develop an intense lipemia as evidenced by marked increases in serum phospholipide, free cholesterol, ester cholesterol, neutral fat, and total fatty acids. The total fatty acid content of the lung, liver, and spleen, however, remains unchanged. No qualitative change in the fatty acids of the lung and liver from treated animals could be detected by the methods used. The injection of triton was found to diminish slightly the cholesterol content of the adrenal glands. The implications of these findings are discussed in relation to an understanding of the mechanism involved in the therapeutic action of triton in experimental tuberculosis.
Guinea pig red cells exposed to triton WR-1339 either in vitro or in vivo demonstrate an increased sensitivity to hemolysis by thermal shock. Although the sensitivity of guinea pig leucocytes to thermal shock remains unchanged after a single injection of triton, their resistance to disruption by acetone and by sonic vibration is increased significantly. Resistance to sonic vibration appears to be maximum within a few hours after injection and then it gradually wanes. Paraffin oil-induced peritoneal exudate cells (monocytes) and leucocytes from whole blood are rendered more resistant to disruption by sonic vibration when exposed to triton in vitro. These findings are discussed briefly in relation to the therapeutic effect of triton in experimental tuberculosis.
The administration of triton WR-1339 (300 mg./kg. subcutaneously) to tuberculin-sensitive guinea pigs 2 hours before the intradermal injection of PPD depresses slightly their skin sensitivity to tuberculin and essentially obliterates the lytic effect of tuberculin on their circulating leucocytes. When leucocytes from tuberculin-sensitive guinea pigs are exposed to triton in vitro at a concentration level attainable in vivo the cells are partially protected against lysis by PPD.
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