title: Block by amiloride derivatives of odor-evoked discharge in lobster olfactory receptor neurons through action on a presumptive TRP channel.
abstract: Amiloride and its derivatives inhibit a number of sensory transduction processes, including some types of chemosensory transduction. Here, we report that pyrazine derivatives of amiloride reversibly inhibit odorant-evoked activity in lobster olfactory receptor neurons. The potency sequence is as follows-(IC50, mM): 5-(N,N-hexamethylene)amiloride (0.015) approximately 5-(N-methyl-N-isobutyl)amiloride (0.02) approximately 5-(N-ethyl-N-isopropyl)amiloride (0.03) > 5-(N,N-dimethyl)amiloride (0.48); 3',4'-dichlorobenzamil (0.4), phenamil (0.5), and amiloride itself (2) are ineffective. The same derivatives with the similar potency sequence also block a presumptive transient receptor potential (TRP) channel that is the likely downstream target of phosphoinositide signaling in these cells. Our results suggest that pyrazine derivatives of amiloride are useful probes to study more detailed mechanisms of chemosensory transduction in this system and possibly in other chemosensory systems in which TRP channels are the known or suspected downstream effector.
authors.affiliation: Whitney Laboratory for Marine Bioscience, Center for Smell and Taste and McKnight Brain Institute, University of Florida, Gainesville, FL 32080-8610 , USA. bobkov@whitney.ufl.edu
authors.forename: Y V
authors.initials: YV
authors.lastname: Bobkov
authors.forename: B W
authors.initials: BW
authors.lastname: Ache
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D020128:Inhibitory Concentration 50; D008121:Nephropidae; D009812:Odorants; D018034:Olfactory Receptor Neurons / Q000502:physiology*; D011719:Pyrazines; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D050051:Transient Receptor Potential Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D011719:Pyrazines; D050051:Transient Receptor Potential Channels; D000584:Amiloride