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.