title: Inositol(1,4,5)trisphosphate signal triggers a receptor-mediated ATP release.
abstract: Intracellular signal transduction pathways involved in ATP release evoked by angiotensin II (Ang II) were investigated in cultured guinea pig Taenia coli smooth muscle cells. Ang II (0.3-1 microM) elicited substantial release of ATP from the cells, but not from a human fibroblast cell line. However, Ang II even at 10 microM failed to cause a leakage of lactate dehydrogenase (LDH) from the smooth muscle cells. The release of ATP by Ang II was suppressed by 10 microM SC52458, an AT1 receptor antagonist, not by 10 microM PD123319, an AT2 receptor antagonist. The evoked release of ATP was almost completely inhibited in the presence of 10 microM U73122, a phospholipase C inhibitor, and 0.5 microM thapsigargin, a Ca2+-ATPase inhibitor. Furthermore, the release was hampered by 50 microM BAPTA/AM, an intracellular Ca2+ chelator, but not by 0.1 microM nifedipine, a voltage gated Ca2+ channel inhibitor. The basal release of ATP was increased by BAPTA/AM, but was reduced by U-73122. Ang II enhanced instantaneously inositol(1,4,5)trisphosphate (Ins(1,4,5)P3) accumulation in the cells. The enhancing effect was perfectly antagonized by SC52458. These findings suggest that intracellular Ca2+ signals activated via stimulation of Ins(1,4,5)P3 receptor are involved in the release of ATP evoked by Ang II.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan. katsurag@fukuoka-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuragi
authors.forename: Chiemi
authors.initials: C
authors.lastname: Sato
authors.forename: Lou
authors.initials: L
authors.lastname: Guangyuan
authors.forename: Kenji
authors.initials: K
authors.lastname: Honda
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D006168:Guinea Pigs; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D018160:Receptors, Cytoplasmic and Nuclear; D013777:Tetrazoles; C084927:forasartan; D000804:Angiotensin II; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate