Odorant-sensitive adenylate cyclase may mediate olfactory reception

Abstract

The mechanism of the sense of smell has long been a subject for theory and speculation1–5. More recently, the notion of odorant recognition by stereospecific protein receptors has gained wide acceptance6–11, but the receptor molecules remained elusive9–15. The recognition molecules are believed to be quite diverse9,11,13–15, which would partly explain the unusual difficulties encountered in their isolation by conventional ligand-binding techniques12,13. An alternative approach would be to probe the receptors through transductory components that may be common to all receptor types7–9,12–14. Here we report the identification of one such transductory molecular component. This is an odorant-sensitive adenylate cyclase, present in very large concentrations in isolated dendritic membranes of olfactory sensory neurones. Odorant activation of the enzyme is ligand and tissue specific, and occurs only in the presence of GTP, suggesting the involvement of receptor(s) coupled to a guanine nucleotide binding protein (G-protein)15–19. The olfactory G-protein is independently identified by labelling with bacterial toxins, and found to be similar to stimulatory G-proteins in other systems17–19. Our results suggest a role for cyclic nucleotides in olfactory transduction13,20–22, and point to a molecular analogy between olfaction and visual15,16, hormone17,18 and neurotransmitter19 reception. Most importantly, the present findings reveal new ways to identify and isolate olfactory receptor proteins.

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Pace, U., Hanski, E., Salomon, Y. et al. Odorant-sensitive adenylate cyclase may mediate olfactory reception. Nature 316, 255–258 (1985). https://doi.org/10.1038/316255a0

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