title: Endoplasmic reticulum is a key organella in bradykinin-triggered ATP release from cultured smooth muscle cells.
abstract: ATP has broad functions as an autocrine/paracrine molecule. The mode of ATP release and its intracellular source, however, are little understood. Here we show that bradykinin via B(2)-receptor stimulation induces the extracellular release of ATP via the inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)]-signaling pathway in cultured taenia coli smooth muscle cells. It was found that bradykinin also increased the production of Ins(1,4,5)P(3) and 2-APB-inhibitable [Ca(2+)](i). The evoked release of ATP was suppressed by the Ca(2+)-channel blockers, nifedipine, and verapamil. Moreover, the extracellular release of ATP was elicited by photoliberation of Ins(1,4,5)P(3). Bradykinin caused a quick and transient accumulation of intracellular ATP from cells treated with 1% perchloric acid solution (PCA), but not with the cell lysis buffer. Peak accumulation was prevented by 2-APB and thapsigargin, but not by nifedipine or verapamil, inhibitors of extracellular release of ATP. These findings suggest that bradykinin elicits the extracellular release of ATP that is mediated by the Ins(1,4,5)P(3)-induced Ca(2+) signaling and, finally, leads to a Ca(2+)-dependent export of ATP from the cells. Furthermore, the bradykinin-induced transient accumulation of ATP in the cells treated with PCA may imply a possible release of ATP from the endoplasmic reticulum.
authors.affiliation: Department of Pharmacology, School of Medicine, Fukuoka University, Japan.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Keisuke
authors.initials: K
authors.lastname: Migita
authors.forename: Chiemi
authors.initials: C
authors.lastname: Sato
authors.forename: Sadaharu
authors.initials: S
authors.lastname: Usune
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuragi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001593:Benzyl Compounds / Q000494:pharmacology; D001896:Boron Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D004963:Estrenes / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D053778:Thiazolidines / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology