Role of phospholipase C in chlorphentermine-induced pulmonary phospholipidosis in rat.
Daily, oral administration of chlorphentermine (60 mg/kg) for 5 days to rats produced a significant increase in the concentration of whole lung total phospholipid as well as sphingomyelin, phosphatidylserine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, and phosphatidylcholine. Similarly, a significant elevation in total and all individual phospholipid components was found in the lysosomal fraction of chlorphentermine-treated rat lung. In contrast, the activities of pulmonary Na+,K+-ATPase and alkaline phosphatase, enzymatic markers of membrane function, were not markedly affected by chlorphentermine treatment. The observed lung phospholipidosis was accompanied by inhibition of phospholipase C activity. Regardless of the phospholipid substrate, chlorphentermine significantly decreased pulmonary phospholipase C to approximately the same extent. Our data show that accumulation of phospholipid in whole lung and lysosomes is associated with an inhibition of phospholipase C activity.
Kacew
S
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Department of Pharmacology, Faculty of Health Sciences, School of Medicine, University of Ottawa, Ontario, Canada.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002745:Chlorphentermine / Q000008:administration & dosage; D008064:Lipidoses / Q000139:chemically induced* / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008171:Lung Diseases / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D010645:Phentermine / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism*
D010645:Phentermine; D000469:Alkaline Phosphatase; D010738:Type C Phospholipases; D000254:Sodium-Potassium-Exchanging ATPase; D002745:Chlorphentermine