Editors' ChoiceOlfaction

An adenosine receptor for olfaction

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Science Signaling  06 Jun 2017:
Vol. 10, Issue 482, eaan8752
DOI: 10.1126/scisignal.aan8752

Extracellular processing of ATP in the fish olfactory epithelium produces adenosine that is perceived by olfactory neurons.

Nucleotides stimulate excitatory responses in the olfactory circuits of fish and frogs, and nucleotides released from food sources have been proposed to attract aquatic vertebrates. Wakisaka et al. found that adenosine triphosphate (ATP) attracted zebrafish, activated a subset of olfactory neurons in the nose, and activated a single glomerulus in the olfactory bulb of the brain. The ATP-responsive olfactory neurons lacked zebrafish olfactory receptors, but expressed A2c, which encodes a putative adenosine receptor. A2c is related to other vertebrate adenosine receptors but was found only in fish and amphibians. A2c overexpressed in CHO cells was activated by adenosine but not by ATP. To identify enzymes that might convert ATP to adenosine in olfactory epithelium, the authors examined the expression of ectonucleotidase-encoding genes in zebrafish. CD73, which encodes an ectonucleotidase that converts adenosine monophosphate (AMP) to adenosine, was expressed in A2c+ neurons. TNAP, which encodes an ectonucleotidase that converts ATP to adenosine in a stepwise fashion, was expressed in nearby nonneuronal cells of the olfactory epithelium. Coexpression of TNAP or CD73 with A2c in CHO cells enabled ATP to stimulate signaling downstream of A2c. In ex vivo preparations of zebrafish brains with the nose attached, pharmacological inhibition of TNAP or CD73 prevented ATP or AMP from activating the glomerulus involved in the attraction of fish to ATP, but these inhibitors did not affect activation of the glomerulus by adenosine. An adenosine receptor inhibitor prevented activation of the glomerulus in response to ATP, AMP, or adenosine. Thus, extracellular enzymatic processing of ATP produces adenosine that is perceived by olfactory neurons through the adenosine receptor A2c. Adenosine receptors have well-documented roles in the heart and in the brain, but had not previously been reported to act as odorant receptors.

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