Hypoxanthine Effect on Equilibrative and Concentrative Adenosine Transport in Human Lymphocytes. Implications in the Phatogenesis of Lesch-Nyhan Syndrome

Abstract

We postulated that increased levels of hypoxanthine, a main characteristic of hypoxanthine phosphoribosyltransferase (HPRT) deficiency, may influence adenosine function which could be related to some of the neurological features of the Lesch-Nyhan syndrome. We have examined the effect of hypoxanthine on different adenosine transporters in peripheral blood lymphocytes from control subjects. Increased hypoxanthine concentrations (25 μM) significantly decreased adenosine transport. The equilibrative adenosine transporters (79.6% of the adenosine transport), both NBTI sensitive and NBTI insensitive, were affected significantly. In contrast, the concentrative adenosine transporters were not influenced by hypoxanthine. These results supports the hypothesis that increased hypoxanthine levels influence equilibrative (predominantly NBTI-insensitive type) adenosine transporters.

Keywords:

• Lesch Nyhan
• HPRT
• Adenosine
• ENT
• CNT
• Hypoxanthine

Acknowledgments

This work was supported by a Medical Scholar Contract from the Subdirección General de Investigación Sanitaria of the Instituto de Salud Carlos III, Health Ministry, Spain, for professionals with a sanitary especialty (to CP, CM, 0300015) and the Network of the Genetic Metabolic diseases (REDEMETH, G 03/054).