False positives from impurities result in incorrect functional characterization of receptors in chemosensory studies

Schorkopf, Dirk Louis P. and Molnár, Béla Péter and Solum, Marit and Larsson, Mattias C. and Millar, Jocelyn G. and Kárpáti, Zsolt and Dekker, Teun (2019) False positives from impurities result in incorrect functional characterization of receptors in chemosensory studies. Progress in Neurobiology, 181. p. 101661. ISSN 03010082

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Abstract

The discovery of chemoreceptors and technological advances have greatly increased our understanding of chemosensory mechanisms. However, some of this rapid progress may have been severely compromised by insufficient attention given to the possible effects of impurities in the chemical standards used in identifying ligands for target receptors. Here, we show that even trace amounts of impurities in test stimuli can completely obscure true ligand-receptor relationships. Responses to impurities may go unrecognized because of two main factors. First, the sensitivity of receptors to ligands may be greater than that of the instruments used to check sample purity. Second, the concentrations of impurities actually reaching the chemoreceptor during experiments may be orders of magnitude higher than that of the putative stimulus, due to large differences in vapour pressure between the impurities and the putative stimulus. Errors caused by impurities are not limited to receptor-ligand studies, but can also affect related areas of chemosensory research, such as neural processing, downstream behaviours, and “in-silico” bioinformatics predictions of response profiles. The purity of standards is always implied but must be checked rigorously to prevent skewed or invalid results or conclusions, such as we exemplify here for Drosophila melanogaster and its olfactory receptor DmOr7a.

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