Effect of chronic renal failure with and without secondary hyperparathyroidism on the activities of synaptosomal tyrosine hydroxylase and monoamine oxidase.
Norepinephrine (NE) content, release and uptake by brain synaptosomes are reduced in chronic renal failure (CRF), and this has been attributed to the state of secondary hyperparathyroidism. The decrease in NE content in CRF could not be explained by changes in NE uptake or release since in normal circumstances, NE content usually remains unchanged despite fluctuation in NE uptake and release. Since NE content is determined by its production and degradation, we examined the effect of CRF with and without excess parathyroid hormone (PTH) on the Michaelis-Menton constant (Km) and Vmax of tyrosine hydroxylase (TH), the rate-limiting enzyme for NE production, and monoamine oxidase (MAO), an enzyme involved in NE degradation of brain synaptosomes. Brain synaptosomes from rats with a 21-day CRF have a significantly (p less than 0.01) lower Vmax of TH (39.5 +/- 5.3 pmol tritiated H2O/mg protein/min) than that of normal rats (61. +/- 7.5 pmol tritiated H2O/mg protein/min) and a higher Km of MAO (59 +/- 2.9 nM tyramine) than normal animals (46 +/- 1.7 nM tyramine). Parathyroidectomy (PTX) in CRF rats normalized Vmax of TH (54 +/- 4.5 pmol tritiated H2O/mg protein) and Km of MAO (48.4 +/- 2.3 nM tyramine). Cytosolic calcium, [Ca2+]i, in brain synaptosomes is significantly (p less than 0.01) higher in rats with CRF (488 +/- 8.5 nM) than in normal (355 +/- 6.0 nM) or PTX-CRF (360 +/- 8.1 nM) rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, University of Southern California School of Medicine, Los Angeles.
A
A
Islam
M
M
Smorgorzewski
M A
MA
Zayed
S G
SG
Massry
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism; D006961:Hyperparathyroidism / Q000150:complications / Q000201:enzymology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009392:Nephrectomy; D009638:Norepinephrine / Q000378:metabolism; D016105:Parathyroidectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013574:Synaptosomes / Q000201:enzymology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D014446:Tyrosine 3-Monooxygenase; D008995:Monoamine Oxidase; D002118:Calcium; D009638:Norepinephrine