Thrombopoietin acts synergistically on Ca(2+) mobilization in platelets caused by ADP or thrombin receptor agonist peptide.
Thrombopoietin (TPO) is the main regulator of megakaryopoiesis and influences also the function of mature platelets. TPO has been shown to synergize in multiple platelet activation processes induced by various agonists. Our aim was to elucidate whether TPO affects calcium signaling during platelet activation processes. TPO demonstrated a synergistic effect on the exocytosis induced by suboptimal doses of adenosine diphosphate (ADP) and the thrombin receptor agonist peptide (TRAP). We detected synergistic effects of TPO on the ADP or TRAP induced Ca(2+) mobilization in a small range of very low agonist concentrations. The TPO synergism on Ca(2+) mobilization and CD62P expression was measurable in different, nonoverlapping ranges of ADP or TRAP concentrations. Sustaining the agonist-induced calcium signal with thapsigargin led to a detectable TPO synergism in CD62P expression even in agonist concentrations in which the synergism only occurs in Ca(2+) signaling without thapsigargin.
Eilers
M
M
Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, D-30623, Germany.
Schulze
H
H
Welte
K
K
Ballmaier
M
M
D000244:Adenosine Diphosphate / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D020013:Calcium Signaling / Q000187:drug effects*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019007:P-Selectin / Q000097:blood; D010446:Peptide Fragments / Q000008:administration & dosage*; D018179:Receptors, Thrombin / Q000819:agonists*; D011994:Recombinant Proteins / Q000008:administration & dosage; D019284:Thapsigargin / Q000494:pharmacology; D013926:Thrombopoietin / Q000008:administration & dosage*
D004791:Enzyme Inhibitors; D019007:P-Selectin; D010446:Peptide Fragments; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; C082835:thrombin receptor peptide (42-47); D000244:Adenosine Diphosphate; D019284:Thapsigargin; D013926:Thrombopoietin; D000252:Calcium-Transporting ATPases; D002118:Calcium