EFFECTS OF ADENOSINE AND CYCLIC NUCLEOTIDES ON 5-PHOSPHORIBOSYL-1-PYROPHOSPHATE(PRPP) SYNTHESIS IN MOUSE SPLENIC LYMPHOCYTES
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The effect of intraperitoneal injection of adenosine 200 mg/kg on the tissue levels of PRPP was investigated in male mice. The liver PRPP level was increased, peaked at 30 min, after adenosine administration. In contrast, the spleen, heart and erythrocyte PRPP levels were decreased. However, the erythrocyte PRPP level began to increase two hours later adenosine administration. A similar increase was observed in the spleen PRPP, but the magnitude was less than that in erythrocytes. Concomitantly, marked decrease of plasma Pi concentration was observed.<BR>The effects of adenosine, inosine a n d guanosine on free and available PRPP concentrations were also investigated in rat and chicken erythrocytes, and mouse splenic lymphocytes in vitro. Under physiological Pi concentrations, these purine nucleosides diminished free and available PRPP concentrations in rat erythrocytes and free PRPP concentration in chicken erythrocytes, but stimulated available PRPP synthesis in chicken erythrocytes. As concerns lymphocytes, the purine nucleosides, especially adenosine, decreased the free PRPP concentration in the presence of physiological Pi concentrations. Available PRPP synthesis was inhibited by adenosine, but not by inosine and guanosine.<BR>Dibutyryl cyclic GMP (Bt<SUB>2</SUB>cGMP) stimulated available PRPP synthesis in the lymphocytes. On the other hand, dibutyryl cyclic AMP (Bt<SUB>2</SUB>cAMP) showed no change in the available PRPP formation. However, Bt2cAMP antagonized the Bt2cGMP response. Adenosine also blocked the Bt<SUB>2</SUB>cGMP effect. ACh as well as Bt<SUB>2</SUB>cGMP enhanced the available PRPP formation in the presence of 1 mM Ca<SUP>++</SUP>, which was antagonized by Bt<SUB>2</SUB>cAMP.<BR>These findings suggest that immunosuppressive effects of adenosine and severe combined immunodeficiency disease with adenosine deaminase deficiency may be explained at least partly from decrease of PRPP synthesis.
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