title: Inward currents and increases in cytosolic Ca2+ concentration induced by cyclic ADP-ribose in turtle olfactory receptor cells.
abstract: In olfactory receptor cells, it is well established that cyclic AMP (cAMP) and inositol-1,4,5-trisphosphate (IP(3)) act as second messengers during odor responses. In previous studies, we have shown that cAMP-increasing odorants induce odor responses even after complete desensitization of the cAMP-mediated pathway. These results suggest that at least one cAMP-independent pathway contributes to the generation of odor responses. In an attempt to identify a novel second messenger, we investigated the possible role of cyclic ADP-ribose (cADPR) in olfactory transduction. Turtle olfactory receptor cells were isolated using an enzyme-free procedure and loaded with fura-2/AM. The cells responded to dialysis with cADPR with an inward current and an increase of the intracellular Ca(2+) concentration, [Ca(2+)](i). Flooding of cells with 100 microM cADPR from the pipette also induced an inward current without changes in [Ca(2+)](i) in Na(+)-containing and Ca(2+)-free Ringer solution. In an Na(+)-free and Ca(2+)-containing Ringer solution, cADPR induced only a small inward current with a concomitant increase in [Ca(2+)](i). Inward currents and increases in [Ca(2+)](i) induced by cADPR were completely inhibited by removal of both Na(+) and Ca(2+) from the outer solution. The experiments suggest that cADPR activates a cation channel at the plasma membrane, allowing inflow of Na(+) and Ca(2+) ions. The magnitudes of the inward current responses to cAMP-increasing odorants were greatly reduced by prior dialyses of a high concentration of cADPR or 8-bromo-cyclic ADP-ribose (8-Br-cADPR), an antagonist. It is possible that the cADPR-dependent pathway contributes to the generation of olfactory responses.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Sekimoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Kashiwayanagi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014426:Turtles
chemical_list: D036563:Cyclic ADP-Ribose; D002118:Calcium