Attenuation of the low-density-lipoprotein-activated phosphoinositide signalling system by calcium blockers in human lymphocytes.
1. The capacity of low-density lipoprotein-cholesterol (40 micrograms/ml) to stimulate both the phosphoinositide cycle and the dislocation of the phospholipid- and calcium-dependent protein kinase C activity from the cytosolic to the membranous compartment in human circulating lymphocytes has been studied. 2. Pretreatment of lymphocytes with pertussis toxin inhibited significantly the low-density-lipoprotein-induced formation of inositol trisphosphate. 3. The calcium-channel blockers verapamil, nifedipine and diltiazem, each in a concentration range from 1 mumol/l to 1 nmol/l, attenuated the low-density lipoprotein-induced formation of inositol trisphosphate in a dose-dependent manner. Similar results were observed when so-called non-specific calcium antagonists, such as flunarizine and molsidomine, were used. 4. The results suggest that low-density lipoprotein activates the phosphoinositide cycle in circulating lymphocytes through mechanisms sensitive to calcium blockers and pertussis toxin.
Locher
R
R
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Sachinidis
A
A
Steiner
A
A
Vetter
W
W
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000494:pharmacology*; D004075:Diglycerides / Q000096:biosynthesis; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008981:Molsidomine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000097:blood*; D011493:Protein Kinase C / Q000097:blood; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D008078:Cholesterol, LDL; D004075:Diglycerides; D010716:Phosphatidylinositols; D014700:Verapamil; D008981:Molsidomine; D011493:Protein Kinase C; D004110:Diltiazem; D009543:Nifedipine; D005444:Flunarizine