cyclic ADP-ribose induced inward currents and increases in cytosolic Ca2+ concentration turtle olfactory receptor cells: a possible role of cADP-riose in olfactory transduction

Abstract

In olfactory receptor cells, it is well established that cAMP and IP₃ act as second messengers during odor responses. We, however, have shown that cAMP-increasing odorants induce odor responses even after complete desensitization of the cAMP-mediated pathway suggesting that at least one cAMP-independent pathways contribute to the generation of odor responses. In attempt to identify a novel second messenger, we investigated the possible role of cyclic ADP-ribose (cADPR) in olfactory transduction. The turtle olfactory cells responded to dialysis with cADPR with an inward current and an increase of the intracellular Ca²⁺ concentration, [Ca²⁺]i. Flooding of cells with 100 μM cADPR from the pipette also induced an inward current without changes in [Ca²⁺]i in Na+-containing and Ca²⁺-free Ringer solution. In a Na+-free and Ca²⁺-containing Ringer solution, cADPR induced only a small inward current with a concomitant increases in [Ca²⁺]i. Inward currents and increase in [Ca²⁺]i induced by cADPR were completely inhibited by removal of both Na⁺ and Ca²⁺ from the outer solution. The experiments suggest that cADPR activates a cation channel at the plasma membrane, allowing inflow of Na⁺ and Ca²⁺ 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. [Jpn J Physiol 54 Suppl:S18 (2004)]