The FASEB Journal, Vol 11, 101-108, Copyright © 1997 by The Federation of American Societies for Experimental Biology

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Ectonucleotidases, purine nucleoside transporter, and function of the bile canalicular plasma membrane of the hepatocyte

M Che, Z Gatmaitan and IM Arias
Department of Molecular and Cellular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

Ectonucleotidases are enzymes that degrade extracellular nucleotides. Extracellular nucleotides (especially ATP) and their degradation products (particularly adenosine) have multiple effects on cell functions by acting through purinergic receptors. Adenosine nucleotides are present in bile, which suggests that hepatocytes may release nucleotides into the canaliculus where they are promptly degraded into adenosine by ecto-ATPase and 5'-nucleotidase, which have been identified in the canalicular plasma membrane. Adenosine is then transported into hepatocytes by a Na+-dependent nucleoside transporter that is present in the canalicular plasma membrane. Purification and molecular cloning of ecto-ATPase and other canalicular proteins are complicated by an abundant canalicular plasma membrane protein, cCAM 105. However, the recent cloning of an ecto-ATPase (apyrase) from potato tubers provides a new opportunity to identify the canalicular ecto-ATPase. The canalicular Na+-dependent purine nucleoside transporter has been cloned from rat liver. Study of its expression during development and other physiological circumstances suggests that the transporter may play an important role in maintaining hepatic purine levels that are essential for the liver to serve as a major source of purines for tissues (i.e., brain, muscle) that lack pathways for de novo purine biosynthesis.

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