Human erythrocytes contain Ca2+, calmodulin-dependent cyclic nucleotide phosphodiesterase which is involved in the hydrolysis of cGMP.
To determine whether phosphodiesterase (PDE) is involved in the degradation of cGMP in human erythrocytes, we studied the cell cGMP content in the presence of different PDE inhibitors: zaprinast and dipyridamole, specific inhibitors of cGMP-binding, cGMP-specific PDE (cG-BPDE); vinpocetine, a specific inhibitor of Ca2+, calmodulin-dependent phosphodiesterase (CaM-PDE); an unspecific inhibitor, 3-isobutyl-1-methylxanthine (IBMX). IBMX, zaprinast, and dipyridamole at 30 microM did not affect the intracellular cGMP content. However, vinpocetine at this concentration increased the cGMP content by 102 +/- 14% (p < 0.05). The effect of vinpocetine was dose-dependent, reached the maximal level after 1 min of incubation and flattened at the same level. Ca2+ (10 microM) in the presence of the Ca(2+)-ionophore, A23187 (5 microM), decreased the cGMP content (-23% +/- 4; p < 0.05), which can be explained by the CaM-PDE activation. The Ca(2+)-induced decrease in cGMP was completely inhibited by the CaM antagonist, W-7 (100 microM). These data suggest that erythrocytes contain Ca2+, CaM-PDE.
Petrov
V
V
Department of Molecular and Cardiovascular Research, University of Leuven, Belgium.
Fagard
R
R
Lijnen
P
P
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D014748:Vinca Alkaloids / Q000494:pharmacology
D002147:Calmodulin; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D013449:Sulfonamides; D014748:Vinca Alkaloids; C013983:vinpocetine; C017967:W 7; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine