Physiological Evidence for the Discrimination ofl-Arginine From Structural Analogues by the Zebrafish Olfactory System

Abstract

Although it is generally assumed that fish are capable of discriminating amino acid odorants on the basis of differences in side-chain structure, less is known about their ability to discriminate amino acids with modifications to α-carboxyl and α-amino groups. In this study, the ability of the zebrafish olfactory system to detect and presumably discriminate analogues of the basic amino acid Arg was assessed, by using cross-adaptation and activity-dependent labeling techniques. Electrophysiological recordings established that esterification (l-arginine methyl ester; AME) or deletion (agmatine or amino-4-guanidobutane; AGB) of the α-carboxyl group yielded odorants more potent than Arg, whereas deletion of the α-amino group (l-argininic acid; AA) yielded a less potent analogue. In cross-adaptation experiments, no test-competitor odorant combination yielded complete cross-adaptation, suggesting the detection of these Arg analogues by multiple odorant receptors (ORs) with partially nonoverlapping specificities. Activity-dependent immunocytochemical labeling of olfactory receptor neurons supported this conclusion. AGB, an ion-channel–permeant probe (and odorant), labeled 4.9 ± 0.4% ( n = 24) of sensory epithelium, whereas the addition of Arg, 1-ethylguanidine sulfate, l-α-amino-β-guanidinopropionate, or AME to AGB resulted in a significant elevation of labeling (8–14%). This study provides evidence that the olfactory system has the potential to discriminate among amino acid odorants with modified α-carboxyl and α-amino groups.