title: Drugs affecting phospholipase C-mediated signal transduction block the olfactory cyclic nucleotide-gated current of adult zebrafish.
abstract: 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 microM), or a PLC inhibitor, neomycin (50 microM), 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.
authors.affiliation: Department of Physiology, University of Utah School of Medicine, Salt Lake City, Utah 84108, USA.
authors.forename: L
authors.initials: L
authors.lastname: Ma
authors.forename: W C
authors.initials: WC
authors.lastname: Michel
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D003545:Cysteine / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009297:Nasal Mucosa / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009355:Neomycin / Q000494:pharmacology; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D012430:Ruthenium Red / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013656:Taurocholic Acid / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D007473:Ion Channels; D012430:Ruthenium Red; D013656:Taurocholic Acid; D000242:Cyclic AMP; D010738:Type C Phospholipases; D009355:Neomycin; D003545:Cysteine