Nicotine downregulates alpha 2 isoform of Na,K-ATPase at the blood-brain barrier and brain in rats.
Effects of chronic nicotine treatment on the relative levels of expression of Na,K-ATPase alpha and beta subunit isoforms were determined in rat cerebral microvessels and capillary-depleted brain homogenates by Western blot analysis. Nicotine, 4.5 mg/kg/day, was administered s.c. by osmotic mini-pumps for 14 days. Expression of alpha 2 isoform in microvessels and brains of nicotine-treated rats was reduced to 0.26 and 0.58 of control levels, respectively. Expression of alpha 1, alpha 3, beta 1 or beta 2 was unchanged. Nicotine decreased cerebromicrovascular and brain Na,ATPase enzymatic activities by 22% and 17%, respectively. It is suggested that chronic exposure to nicotine reduces expression of functional Na,K-ATPase at the blood-brain barrier and brain by downregulating the alpha 2 isoform.
Wang
L
L
Department of Neurologic Surgery, Childrens Hospital Los Angeles, USC School of Medicine 90033.
McComb
J G
JG
Weiss
M H
MH
McDonough
A A
AA
Zlokovic
B V
BV
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000201:enzymology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002196:Capillaries / Q000187:drug effects / Q000201:enzymology; D002560:Cerebrovascular Circulation; D005260:Female; D015870:Gene Expression; D007527:Isoenzymes / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*
D007527:Isoenzymes; D009538:Nicotine; D000254:Sodium-Potassium-Exchanging ATPase