Hydroxyurea stimulates the release of ATP from rabbit erythrocytes through an increase in calcium and nitric oxide production.

European Journal of Pharmacology
Madushi RaththagalaDana M Spence

Abstract

Hydroxyurea, a proven therapy for sickle cell disease, is known to improve blood flow and reduce vaso-occlusive crises, although its exact mechanism of action is not clear. The objective of this study was to determine if hydroxyurea results in an increase of ATP release from the red blood cell (RBC) via the drug's ability to stimulate nitric oxide (NO) production in these cells. A system enabling the flow of RBCs through microbore tubing was used to investigate ATP release from the RBC. Incubation of rabbit RBCs (7% hct) with 50 microM hydroxyurea resulted in a significant increase in the release of ATP from these cells. This level of ATP release was not detected in the absence of flow. Studies also showed that increments in hydroxyurea and NO (from spermine NONOate) resulted in an initial increase in ATP release, followed by a decrease in this release at higher concentrations of hydroxyurea and the NO donor. Incubation with L-NAME abolished the effect of the hydroxyurea, suggesting that NO production by the RBC was involved. Indeed, in the presence of 50 microM hydroxyurea, the amount of total Ca(2+) measured (by atomic absorption spectroscopy) in a 7% solution of RBCs increased from 363+/-47 ng/ml and 530+/-52 ng/ml. Finally,...Continue Reading

References

Jan 1, 1992·Acta Haematologica·M A el-HazmiM Harakati
Jan 14, 1993·The New England Journal of Medicine·G P RodgersA W Nienhuis
Jun 8, 2001·American Journal of Hematology·Z HuangD B Kim-Shapiro
Jan 11, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Melek Bor-KucukatayOguz K Baskurt
Jan 25, 2003·British Journal of Haematology·Christina Halsey, Irene A Roberts
Feb 7, 2003·Current Medicinal Chemistry·S Bruce King
Mar 29, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Kazuyoshi KirimaToshiaki Tamaki
Apr 12, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Randy S SpragueAndrew J Lonigro
Apr 10, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Jeffrey J OlearczykRandy S Sprague
Aug 12, 2004·Free Radical Biology & Medicine·S Bruce King
Feb 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·John R PawloskiJonathan S Stamler
Dec 22, 2005·Blood·Petra KleinbongardMalte Kelm
Mar 7, 2006·The International Journal of Biochemistry & Cell Biology·A Kyle Mack, Gregory J Kato
Mar 11, 2006·Blood·Vladan P CokicAlan N Schechter
Oct 31, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Andrei L KleschyovThomas Munzel
Mar 28, 2008·The New England Journal of Medicine·Orah S Platt
Aug 25, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Zeling CaoJoseph M Rifkind

❮ Previous
Next ❯

Citations

May 27, 2014·PloS One·Cora Lilia AlvarezPablo Julio Schwarzbaum
Feb 18, 2014·Nitric Oxide : Biology and Chemistry·Sarah Y LockwoodDana M Spence
Nov 4, 2015·Nitric Oxide : Biology and Chemistry·Patrick KirbyDov Jaron
Aug 12, 2015·Purinergic Signalling·Geoffrey Burnstock
Dec 3, 2013·Integrative Biology : Quantitative Biosciences From Nano to Macro·Yimeng WangDana M Spence

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.