title: Verapamil corrects abnormalities in norepinephrine metabolism of brain synaptosomes in CRF.
abstract: Abnormalities in norepinephrine (NE) metabolism of brain synaptosomes occur in chronic renal failure (CRF), and this has been attributed to the parathyroid hormone (PTH)-induced accumulation of calcium in synaptosomes. The present study examined the effect of treatment with the calcium-channel blocker verapamil on NE content, release, and uptake, on Na(+)-K(+)-ATPase activity, and on calcium content of brain synaptosomes from rats with 21 days of CRF. Verapamil treatment of normal rats for 21 days did not affect synaptosomal NE content, release, or uptake, Na(+)-K(+)-ATPase activity, or calcium content. Rats with 21 days of CRF displayed a significant (P less than 0.01) reduction in their synaptosomal NE content, release, and uptake, an increase in Na(+)-K(+)-ATPase activity, and a significant (P less than 0.01) increase in calcium content of synaptosomes. The treatment of CRF rats with verapamil normalized synaptosomal NE content and release and Na(+)-K(+)-ATPase activity, produced a significant (P less than 0.01) improvement in NE uptake, and prevented the accumulation of calcium in synaptosomes. The data of the present study are consistent with the notion that the abnormalities in synaptosomal NE metabolism and Na(+)-K(+)-ATPase in CRF are mainly the result of PTH-induced accumulation of calcium in synaptosomes and could be prevented by a calcium-channel blocker.
authors.affiliation: Division of Nephrology, University of Southern California, School of Medicine, Los Angeles 90033.
authors.forename: M
authors.initials: M
authors.lastname: Smogorzewski
authors.forename: A
authors.initials: A
authors.lastname: Islam
authors.forename: R
authors.initials: R
authors.lastname: Minasian
authors.forename: A R
authors.initials: AR
authors.lastname: Soliman
authors.forename: S G
authors.initials: SG
authors.lastname: Massry
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D009638:Norepinephrine