Cyclic nucleotide metabolism in the
human erythrocyte
De Bari, V.A., Novak, N.A. and Bennun, A.
Erythrocytes, which show little or no guanylate or adenylate
cyclase activity, take up cyclic nucleotides from blood. Studies
were done by incubating human erythrocytes in isotonic medium
with the dibutyryl derivatives of cAMP and cGMP and in a hypotonic
medium in which the cells are partially hemolyzed and, therefore,
freely permeable to cAMP and cGMP. At cAMP and cGMP concentrations
of 50 µM and above, the amount of 14CO2 generated from
1-14C-glucose was decreased significantly. This effect was
suppressed by 4.6 mM theophylline. Inosine and ribose, which
are catabolites of cAMP and cGMP also decreased formation
of 14CO2 from 1-14C-glucose. Accordingly, it is postulated
that in the absence of theophylline, the activity of phosphodiesterase
resulted in AMP and GMP forma¬tion. These mononucleotides
enter into the purine salvage pathways to form ribose phos¬phate.
Additionally, the production of lactate and 2,3-diphosphoglycerate
(2,3-DPG) was measured in human erythrocytes after incubation
with the dibutyryl derivatives of cAMP (bt2-cAMP) and cGMP
(bt2-cGMP). At a concentration of 0.1 µM, bt2-cGMP inhibits
lactate production at 60 min (p < 0.01). Slight increases
in 2,3-DPG were not statistically significant. Catabolism
of cyclic nucleotides may prevent diffusion equilibria allowing
for the erythro¬cyte's continuous uptake of cyclic nucleotides
and providing a detoxification mechanism that could compensate
for conditions in which elevations of these substances are
observed.
Clinical Physiology and Biochemistry, 2, (1984), 227-238