Hypolipidemic activity of dipyridamole: effects on the main regulatory enzyme of cholesterogenesis.
The in vivo dipyridamole treatment for 16 days produced a significant decrease in chick plasma cholesterol, mainly due to the esterified form. This effect was especially patent in the VLDL + LDL fraction. Similar results were observed in triglyceride content. To our knowledge, this is the first report on this hypolipidemic effects of dipyridamole. Total and esterified cholesterol increased after the same treatment in chick liver, while brain cholesterol content was not affected. Hepatic 3-hydroxy-3- methylglutaryl-CoA reductase activity was drastically reduced, while other secondary regulatory enzymes such as mevalonate kinase, mevalonate 5-phosphate kinase and mevalonate 5-pyrophosphate decarboxylase did not change significantly. No significant differences were found in cholesterol and lipidic phosphorus from liver microsomes, so that the effect of dipyridamole on reductase activity cannot be due to modifications in cholesterol/lipidic phosphorus molar ratio. Neither of these enzyme activities was affected in vitro by dipyridamole.
Zafra
M F
MF
Department of Biochemistry and Molecular Biology, University of Granada, Spain.
Fernandez-Becerra
M
M
Castillo
M
M
Burgos
C
C
Garcia-Peregrin
E
E
D000818:Animals; D002262:Carboxy-Lyases / Q000378:metabolism; D002645:Chickens; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D004176:Dipyridamole / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D000960:Hypolipidemic Agents; D008297:Male; D008862:Microsomes, Liver / Q000737:chemistry / Q000187:drug effects; D010770:Phosphotransferases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor); D017856:Phosphotransferases (Phosphate Group Acceptor)
D000960:Hypolipidemic Agents; D004176:Dipyridamole; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase; D017856:Phosphotransferases (Phosphate Group Acceptor); C022371:phosphomevalonate kinase; D002262:Carboxy-Lyases; C022503:pyrophosphomevalonate decarboxylase