2001 Fiscal Year Final Research Report Summary
A novel olfactory transdution pathway mediated via cADP-ribose
| Project/Area Number |
12672083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
KASHIWAYANAGI Makoto Hokkaido Univ., Sch. of Pharm. Sci, Associate Prof., 大学院・薬学研究科, 助教授 (20169436)
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| Project Period (FY) |
2000 – 2001
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| Keywords | CADP-ribose / CAMP / IR / odor / olfactory cell / second messenger / Ca^<2-1> / effectrophysiology |
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| Research Abstract |
In olfactory neurons, it is well established that cAMP and/or IP_3 act as second messengers during odor responses. We previously showed that one or more both cAMP- and IP_3 independent pathways contribute to the generation of odor responses. The present study explores the role of cADPR in the olfactory transduction pathway. Turtle olfactory receptor cells were isolated with an enzyme-free procedure and loaded with fura-2/AM from the bath solution. The cells responded to dialysis with cADP-ribose with an inward current, an increase in membrane conductance and an increase of the intracellular Ga^<2+> concentration, [Ca^<2+]>_i. Dialysis of cADP-ribose induced inward currents in a dose-dependent manner. Flooding of cells with 100μM cADP-ribose from the pipette also induced an inward current without changes in [Ca^<2+>]_i in Ca^<2+>-free Ringer solution. In Na^+-free Ringer solution, cADPR induced only small inward currents with increases in [Ca^<2+>]_i. Inward currents and increase in [Ca^<2+>]_i induced by cADP-ribose were completely inhibited by removal of both Na^+ and Ca^<2+> from the outer solution. The experiments suggest that cADP-ribose 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 previous dialyses of a high concentration of cADP-ribose or 8-Br-cADP-ribose: an antagonist, suggesting that the cADP-ribose-dependent pathway greatly contributes to the generation of olfactory responses.
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