Drugs Affecting Phospholipase C-Mediated Signal Transduction Block the Olfactory Cyclic Nucleotide-Gated Current of Adult Zebrafish

Abstract

Ma, Li and William C. Michel. Drugs affecting phospholipaseC-mediated signal transduction block the olfactory cyclic nucleotide-gated current of adult zebrafish. J. Neurophysiol. 79: 1183–1192, 1998. Amino acid and bile salt odorants are detected by zebrafish with relatively independent odorant receptors, but the transduction cascade(s) subsequently activated by these odorants remains unknown. Electro-olfactogram recording methods were used to determine the effects of two drugs, reported to affect phospholipase C (PLC)/inositol tripohsphate (IP3)-mediated olfactory transduction in other vertebrate species, on amino acid and bile salt-evoked responses. At the appropriate concentrations, either an IP3-gated channel blocker, ruthenium red (0.01–0.1 μM), or a PLC inhibitor, neomycin (50 μM), reduced amino-acid–evoked responses to a significantly greater extent than bile salt-evoked responses. Excised patch recording techniques were used to measure the affects of these drugs on second-messenger–activated currents. Ruthenium red and neomycin are both effective blockers of the olfactory cyclic nucleotide-gated (CNG) current. Both drugs blocked the CNG channel in a voltage-dependent and reversible manner. No IP3-activated currents could be recorded. The differential effects of ruthenium red and neomycin on odor-evoked responses suggest the activation of multiple transduction cascades. The nonspecific actions of these drugs on odor-activated transduction pathways and our inability to record an IP3-activated current do not permit the conclusion that zebrafish, like other fish species, use a PLC/IP3-mediated transduction cascade in the detection of odorants.