Regular Article
Nicotine Downregulates α2 Isoform of Na,K-ATPase at the Blood-Brain Barrier and Brain in Rats

https://doi.org/10.1006/bbrc.1994.1389Get rights and content

Abstract

Effects of chronic nicotine treatment on the relative levels of expression of Na,K-ATPase α and β 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 α2 isoform in microvessels and brains of nicotine-treated rats was reduced to 0.26 and 0.58 of control levels, respectively. Expression of α1, α3, β1 or β2 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 α2 isoform.

References (0)

Cited by (27)

  • Estrogen-progestin oral contraceptive and nicotine exposure synergistically confers cardio-renoprotection in female Wistar rats

    2020, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    However, NIC-exposed rats with cardiometabolic dysregulation did not have any alteration in cardiac Na+/K+-ATPase activity whereas renal Na+/K+-ATPase activity was not affected by the treatment. The present finding that NIC exposure did not alter cardiac and renal Na+/K+-ATPase activities is not in agreement with studies that associated chronic NIC exposure with decreased Na+/K+-ATPase activity in skeletal muscle and brain of rats [47]. Interestingly COC + NIC treatment led to enhanced cardiac and preserved renal Na+/K+-ATPase activities.

  • Alkali metals levels in the human brain tissue: Anatomical region differences and age-related changes

    2016, Journal of Trace Elements in Medicine and Biology
    Citation Excerpt :

    Inhaled in cigarette smoke, nicotine quickly reaches the brain. Chronic cigarette smoking has shown neuronal membrane damage arising from decreased activity of membrane-bound enzymes (e.g., Na+/K+-ATPase, Ca2+-ATPase, Mg2+-ATPase) in rat brain [45] and reduced expression of functional Na+/K+-ATPase at the blood-brain barrier [46]. Increased levels of K, Rb and Cs found in brain tissue of smokers may be a result of a decreased activity and/or expression of Na+/K+-ATPase, leading to imbalances of electrolytes.

  • Effect of nicotine and polyaromtic hydrocarbons on cerebral endothelial cells

    2008, Cell Biology International
    Citation Excerpt :

    Respecting endothelial barrier function it is of special importance that nicotine is able to reorganize the cytoskeleton of bovine aortic endothelial cells (Cucina et al., 2000) and that nicotine induced upregulation of vascular endothelial growth factor expression in porcine aortic endothelial cells (Conklin et al., 2002). It has also been shown that nicotine increases plasminogen activator inhibitor-1 production by cerebral endothelial cells via a PKC dependent pathway (Zidovetzki et al., 1999) and that nicotine is able to downregulate alpha 2 isoform of Na,K-ATPase at the BBB in rats, which is an important mediator of ion homeostasis in the brain (Wang et al., 1994). Furthermore, an increase in permeability and decrease in ZO-1 expression has been recently demonstrated (Abbruscato et al., 2002; Hawkins et al., 2004).

  • Pathophysiology of the Blood-Brain Barrier: Animal Models and Methods

    2007, Current Topics in Developmental Biology
    Citation Excerpt :

    What is known is that under normal conditions, the ionic composition of brain interstitial fluid is highly resistant to fluctuations in the ionic composition of the blood (Stummer et al., 1995). However, dysregulation of ion transporter expression or activity at the BBB by chronic insults, such as hypertension or nicotine, may predispose individuals to developing postischemic brain edema due to a diminished capacity to respond to sudden changes in interstitial fluid ion content (Abbruscato et al., 2004; Hom et al., 2007; Wang et al., 1994). The capillary endothelium also expresses members of the ATP‐binding cassette (ABC) family that mediate the active efflux of xenobiotics and metabolites from brain to blood.

View all citing articles on Scopus
View full text