Abnormal norepinephrine uptake and release in brain synaptosomes in chronic renal failure.
Abnormalities in the function of the central nervous system exist in chronic renal failure (CRF) and some of these derangements may be related to excess parathyroid hormone (PTH) which causes a rise in brain calcium. The latter may affect metabolism of neurotransmitters such as norepinephrine (NE) in brain synaptosomes. We measured NE content, uptake and release in brain synaptosomes of CRF rats and studied whether excess PTH affects these parameters. Synaptosomes from rats with 21 days of CRF compared to those from normal animals have higher calcium content (11.4 +/- 0.92 vs. 7.1 +/- 0.50 nmol/mg protein, P less than 0.01) and lower Na-K ATPase activity (6.5 +/- 0.81 vs. 11.4 +/- 0.76 mumol Pi/mg protein/hr, P less than 0.01). NE content (11.0 +/- 0.60 vs. 13.6 +/- 0.55 pmol/mg protein/hr, P less than 0.01), uptake (46 +/- 4.5 vs. 110 +/- 5.9 pmol/mg protein times 50 min, P less than 0.01) and release (2.0 +/- 0.2 vs. 5.1 +/- 0.47 pmol/mg protein times 10 min, P less than 0.01). Parathyroidectomy (PTX) in CRF rats kept normocalcemic reversed these abnormalities in brain synaptosomes; indeed calcium content, Na-K ATPase activity and NE content, uptake and release in synaptosomes from PTX-CRF rats were not different from those seen in normal rats.(ABSTRACT TRUNCATED AT 400 WORDS)
Smogorzewski
M
M
Division of Nephrology, University of Southern California School of Medicine, Los Angeles.
Campese
V M
VM
Massry
S G
SG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism
D010281:Parathyroid Hormone; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine