title: Purinoceptors are involved in the induction of an osmolyte permeability in malaria-infected and oxidized human erythrocytes.
abstract: In human erythrocytes, infection by the malaria parasite Plasmodium falciparum or oxidative stress induces a new organic osmolyte and anion permeability. To examine a role for autocrine purinoceptor signaling during this induction process, erythrocytic purinoceptor expression, and ATP release were determined. Furthermore, using pharmacological and genetic approaches the dependence on purinoceptor signaling of osmolyte permeability and Plasmodium development, both in vitro and in vivo, were assessed. Extracellular ATP did not induce an osmolyte permeability in non-infected or non-oxidized erythrocytes. ATP and other purinoceptor agonists increased the induction of osmolyte permeability during infection or oxidation as measured by isosmotic hemolysis and patch-clamp recording. Purinoceptor antagonists and apyrase decreased the induced permeability. The observed pharmacology suggested the involvement of P2Y purinoceptors. Accordingly, human erythrocytes expressed P2Y1 protein. Moreover, P2Y1-deficient mouse erythrocytes exhibited a delayed appearance of the osmolyte permeability during P. berghei infection- or oxidation compared with wild-type erythrocytes. Furthermore, the nonspecific purinoceptor antagonist suramin decreased in vitro growth and DNA/RNA amplification of P. falciparum in human erythrocytes and decreased in vivo growth of P. berghei. P. berghei developed slower in P2Y1-deficient mice in vivo compared with wild-type animals. In conclusion, induction of the osmolyte permeability in Plasmodium-infected erythrocytes involves autocrine purinoceptor signaling.
authors.affiliation: Department of Physiology I, University of Tübingen, Tübingen, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Tanneur
authors.forename: Christophe
authors.initials: C
authors.lastname: Duranton
authors.forename: Verena B
authors.initials: VB
authors.lastname: Brand
authors.forename: Ciprian D
authors.initials: CD
authors.lastname: Sandu
authors.forename: Canan
authors.initials: C
authors.lastname: Akkaya
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kasinathan
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Ronald
authors.initials: R
authors.lastname: Sluyter
authors.forename: Julian A
authors.initials: JA
authors.lastname: Barden
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology*; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D010962:Plasmodium berghei / Q000187:drug effects / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1; D013498:Suramin / Q000494:pharmacology
chemical_list: C546382:P2RY1 protein, human; C546383:P2ry1 protein, mouse; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D013498:Suramin; D000255:Adenosine Triphosphate; D001081:Apyrase