Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells

Joiner, Clinton H.; Jiang, Maorong; Claussen, William J.; Roszell, Nancy J.; Yasin, Zahida; Franco, Robert S.

doi:10.1182/blood.v97.12.3976

Cited by 36 publications

(21 citation statements)

References 35 publications

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“…Though not particularly enlightening, the only clues presently available are its differential properties in SS reticulocytes and discocytes considered above, and the inhibitory effect of stilbene disulfonates (161), suggesting band 3 protein participation in P sickle . Dipyridamole, a widely used antiplatelet agent, with limited side effects, was also shown to inhibit P sickle (165), but no trials have been reported to date.…”

Section: B P Sickle Inhibitionmentioning

confidence: 98%

Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration

Lew¹,

Bookchin²

2005

Physiological Reviews

148

154

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Polymers of deoxyhemoglobin S deform sickle cell anemia red blood cells into sickle shapes, leading to the formation of dense, dehydrated red blood cells with a markedly shortened life-span. Nearly four decades of intense research in many laboratories has led to a mechanistic understanding of the complex events leading from sickling-induced permeabilization of the red cell membrane to small cations, to the generation of the heterogeneity of age and hydration condition of circulating sickle cells. This review follows chronologically the major experimental findings and the evolution of guiding ideas for research in this field. Predictions derived from mathematical models of red cell and reticulocyte homeostasis led to the formulation of an alternative to prevailing gradualist views: a multitrack dehydration model based on interactive influences between the red cell anion exchanger and two K(+) transporters, the Gardos channel (hSK4, hIK1) and the K-Cl cotransporter (KCC), with differential effects dependent on red cell age and variability of KCC expression among reticulocytes. The experimental tests of the model predictions and the amply supportive results are discussed. The review concludes with a brief survey of the therapeutic strategies aimed at preventing sickle cell dehydration and with an analysis of the main open questions in the field.

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Section: B P Sickle Inhibitionmentioning

confidence: 98%

Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration

Lew¹,

Bookchin²

2005

Physiological Reviews

148

154

View full text Add to dashboard Cite

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“…The inhibition of cell dehydration represents a possibility of treatment of SCD. Some agents are known to have such an effect on dehydration: clotrimazole and its metabolite (ICA-17043) are specific inhibitors of the Gardos channel [26][27][28][29][30][31][32] , magnesium pidolate is known to modulate KCl cotransport [6,[33][34][35][36] , NS 3623 is a specific inhibitor of Cl -conductance [6,25,37] , and dipyridamole is an inhibitor of the deoxygenation-induced fluxes [6,38] .…”

Section: Control Ratiomentioning

confidence: 99%

In vitro Inhibitory Effects of Disodium Cromoglycate on Ionic Transports Involved in Sickle Cell Dehydration

et al. 2009

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Background: The antiallergic and antiasthmatic drug disodium cromoglycate (DSCG) has also demonstrated an activity against sickle cell disease, but the mechanism of this action still remains unknown. Methods: Na⁺ and K⁺ fluxes were studied in red cells obtained from 9 patients affected with sickle cell disease in the absence or in the presence of 1 mM of DSCG and deoxygenated under an N₂ flow during up to 24 h. Results: A significant inhibiting effect of DSCG on the intracellular K⁺ exit and the Na⁺ entry was observed. Conclusion: These results demonstrate that DSCG partially inhibits the abnormal K⁺ loss which is implicated in the dehydration of the sickle cell and the stimulation of sickling.

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“…DIDS and dipyridamole are well established inhibitors of P sickle , the deoxygenation-induced cation conductance, in HbS cells [24,25].…”

Section: Resultsmentioning

confidence: 99%

Deoxygenation-Induced Non-Electrolyte Pathway in Red Cells from Sickle Cell Patients

Browning¹,

Robinson²,

Ellory³

et al. 2007

Cell Physiol Biochem

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Red cells from patients with sickle cell disease contain HbS rather than the normal HbA (here termed HbS cells). On deoxygenation, HbS cells exhibit a distinctive solute permeability pathway, P_sickle, activated stochastically, and partially inhibited by DIDS and dipyridamole. It is often referred to as a cation channel although its permeability characteristics remain vague and its molecular identity is unknown. We show that, in contrast to normal red cells, a proportion of HbS cells underwent haemolysis when deoxygenated in isosmotic non-electrolyte solutions. Haemolysis was stochastic: cells unlysed after an initial deoxygenation pulse showed lysis when harvested, reoxygenated and subsequently exposed to a second period of deoxygenation. O₂ dependence of haemolysis was similar to that of P_sickle activation. Haemolysis was accompanied by high rates of sucrose influx, and both haemolysis and sucrose influx were inhibited by DIDS and dipyridamole. Sucrose influx was only detected as ionic strength was reduced below 80 mM. These findings are consistent with the postulate that deoxygenation of HbS cells, under certain conditions, activates a novel non-electrolyte pathway. Their significance lies in understanding the nature of the deoxygenation-induced permeability in HbS cells, together with its relationship with novel pathways induced by a variety of manipulations in normal red cells.

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Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells

Cited by 36 publications

References 35 publications

Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration

Ion Transport Pathology in the Mechanism of Sickle Cell Dehydration

In vitro Inhibitory Effects of Disodium Cromoglycate on Ionic Transports Involved in Sickle Cell Dehydration

Deoxygenation-Induced Non-Electrolyte Pathway in Red Cells from Sickle Cell Patients

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