Control of the Na+,K(+)-ATPase under normal and pathological conditions.
The Na+,K(+)-ATPase is an important enzyme in determining the ionic milieu of the cerebromicrovasculature and neurons. The effect of hypertension or aging on this enzyme, as well as its susceptibility to regulation by fatty acids or aluminum, is the focus of this study. A significant increase (34%) in the apparent affinity constant (KD) but no change in the maximum binding capacity (Bmax) for [3H]ouabain binding to the cerebromicrovascular Na+,K(+)-ATPase occurs after induction of acute hypertension. In addition, long chain unsaturated fatty acids stimulate the binding of [3H]ouabain to the enzyme in microvessels from normotensive and hypertensive rats. The synaptosomal Na+,K(+)-ATPase is sensitive to aluminum. AlCl3 (1-100 microM) inhibits the K(+)-dependent-p-nitrophenylphosphatase (K(+)-NPPase) activity of the Na+,K(+)-ATPase in a dose-dependent manner. AlCl3 (100 microM) decreases the Vmax by 14% but does not alter the KM, suggestive of non-competitive inhibition. The enzyme from aged brain displays a greater Vmax, but shows the same susceptibility to AlCl3 as the enzyme from younger brain. In summary, disruption of the Na+,K(+)-ATPase may underlie, at least in part, abnormalities of nerve and vascular cell function in disorders where elevated concentrations of fatty acids or metal ions are involved.
Caspers
M L
ML
Department of Chemistry, University of Detroit Mercy, MI 48219.
Kwaiser
T M
TM
Dow
M J
MJ
Fu
M J
MJ
Grammas
P
P
D009597:4-Nitrophenylphosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000535:Aluminum / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002196:Capillaries / Q000201:enzymology; D005227:Fatty Acids / Q000494:pharmacology / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010042:Ouabain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D005227:Fatty Acids; D000804:Angiotensin II; D010042:Ouabain; D000535:Aluminum; D005723:gamma-Glutamyltransferase; D009597:4-Nitrophenylphosphatase; D000254:Sodium-Potassium-Exchanging ATPase