Effect of verapamil on CRF-induced abnormalities in phospholipid contents of brain synaptosomes.
Chronic renal failure is associated with significant reductions in total phospholipids, phosphatidylinositol, phosphatidylserine, and phosphatidylethanolamine of brain synaptosomes. These derangements in synaptosomal phospholipid metabolism were attributed to the state of secondary hyperparathyroidism of chronic renal failure (CRF) and the parathyroid hormone-induced accumulation of calcium in synaptosomes. This study examined whether a calcium channel blocker, verapamil, would prevent this synaptosomal calcium accumulation and correct the abnormalities in synaptosomal phospholipids in CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal content of calcium or phospholipids. CRF of 21 days' duration was associated with a significant (P less than 0.01) increase in synaptosomal calcium (10.2 +/- 0.5 vs 7.4 +/- 0.6 nmol/mg protein) and a significant reduction (P less than 0.01) in total phospholipids (397 +/- 12 vs 529 +/- 19 nmol phospholipid P/mg protein), phosphatidylinositol (2.7 +/- 0.22 vs 4.6 +/- 0.27 nmol phospholipid P/mg protein), and phosphatidylserine (37 +/- 1.9 vs 83 +/- 5.2 nmol phospholipid P/mg protein). Simultaneous treatment of CRF rats with verapamil for 21 days reversed the synaptosomal abnormalities in calcium and phospholipid contents. Our data support the notion that the effect of excess parathyroid hormone of CRF on synaptosomal phospholipids is mainly due to the parathyroid hormone-induced calcium accumulation.
Islam
A
A
Division of Nephrology, University of Southern California, School of Medicine, Los Angeles 90033.
Smogorzewski
M
M
Massry
S G
SG
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013574:Synaptosomes / Q000032:analysis*; D014700:Verapamil / Q000494:pharmacology*
D010743:Phospholipids; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium