Regulation of inositol 1,4,5-trisphosphate-induced calcium release by inositol 1,4,5-trisphosphate and calcium in human platelets.
Inositol 1,4,5-trisphosphate (IP3)-induced release of Ca2+, its regulation by IP3 and Ca2+, and the metabolism of IP3 was analyzed in saponin-permeabilized human platelets. At 37 degrees C successive sub-maximal aliquots of IP3 induce a biphasic release of part of the IP3-sensitive Ca2+ pool each time. Although the IP3-induced Ca2+ flux rapidly ceases after addition of IP3, the IP3-sensitive Ca2+ stores regain their sensitivity shortly after stimulation with IP3. Under these conditions IP3 is rapidly hydrolyzed to inositol 1,4-bisphosphate which is unable to release Ca2+. The cooperativity of IP3-induced Ca2+ release and the metabolism of IP3 can account for both the rapid recovery of sensitivity of the IP3-sensitive Ca2+ pool and the partial release induced by sub-maximal concentrations of IP3. The data of the present study favour a steady state rather than an all-or-none mechanism of Ca2+ release.
Department of Research, Kantonsspital, Basel, Switzerland.
M
M
Eberhard
P
P
Erne
D000814:Aniline Compounds; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002118:Calcium / Q000097:blood* / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000097:blood* / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000097:blood; D007700:Kinetics; D015398:Signal Transduction; D014966:Xanthenes
D000814:Aniline Compounds; D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D014966:Xanthenes; C059715:Fluo-3; C044259:inositol 1,4-bis(phosphate); D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium