title: Adenophostin-medicated quantal Ca2+ release in the purified and reconstituted inositol 1,4,5-trisphosphate receptor type 1.
abstract: Kinetics of Ca2+ release by adenophostin, a novel agonist of inositol 1,4,5-trisphosphate (IP3) receptor, in the purified and reconstituted IP3 receptor type 1 (IP3R1) was investigated using the fluorescent Ca2+ indicator fluo-3. Submaximal concentrations of adenophostin caused quantal Ca2+ release from the purified IP3R1 as IP3 did. Adenophostin-induced Ca2+ release by the purified IP3R1 exhibited a high positive cooperativity (nH = 3.9 +/- 0.2, EC50 = 11 nM), whereas the IP3-induced Ca2+ release exhibited a moderate one (nH = 1.8 +/- 0.1, EC50 = 100 nM). Inhibition of [3H]IP3 binding to the purified IP3R1 by adenophostin exhibited a positive cooperativity (nH = 1.9, Ki = 10 nM), whereas IP3 did not (nH = 1.1, Ki = 41 nM).
authors.affiliation: Department of Molecular Neurobiology, University of Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Hirota
authors.forename: T
authors.initials: T
authors.lastname: Michikawa
authors.forename: A
authors.initials: A
authors.lastname: Miyawaki
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Tanzawa
authors.forename: I
authors.initials: I
authors.lastname: Okura
authors.forename: T
authors.initials: T
authors.lastname: Furuichi
authors.forename: K
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000814:Aniline Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D005456:Fluorescent Dyes; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007700:Kinetics; D051379:Mice; D011510:Proteolipids; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000378:metabolism; D014966:Xanthenes
chemical_list: D000814:Aniline Compounds; D015220:Calcium Channels; D005456:Fluorescent Dyes; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011510:Proteolipids; D018160:Receptors, Cytoplasmic and Nuclear; D014966:Xanthenes; C020485:proteoliposomes; C085030:adenophostin B; C059715:Fluo-3; D015544:Inositol 1,4,5-Trisphosphate; D000241:Adenosine; D002118:Calcium