Purinergic signaling negatively regulates activity of an olfactory receptor in an odorant-dependent manner.

Extracellular purines and pyrimidines are important signaling molecules that mediate diverse biological functions via cell surface purinergic receptors. Although purinergic modulation to olfactory activity has been reported, cell-specific expression and action of purinergic receptors deserve further exploration. We physiologically characterized expression of purinergic receptors in a set of olfactory sensory neurons that are responsive to both acetophenone and benzaldehyde (AB-OSNs). Sparsely distributed in the most ventral olfactory receptor zone, AB-OSNs were activated by P2 purinergic receptor agonists but not by P1 purinergic receptor agonist adenosine. Both P2X-selective agonist α,β-methylene ATP and P2Y-selective agonist uridine 5'-triphosphate (UTP) were stimulatory to AB-OSNs, indicating expression of both P2X and P2Y purinergic receptors in AB-OSNs. Pharmacological characterization of receptor specificity using various P2X and P2Y agonists and antagonists illustrated that P2X1 and P2Y2 receptors played major roles in purinergic signaling in AB-OSNs. Interestingly, the results of purinergic modulation to acetophenone-evoked responses were different from those to benzaldehyde-evoked responses within the same neurons. Activation of P2X1 receptors had more profound inhibitory effects on benzaldehyde-evoked intracellular calcium elevation than on acetophenone-evoked responses within the same neurons, and the reverse was true when P2Y2 receptors were activated. Cross-adaptation data showed that acetophenone and benzaldehyde bound to the same olfactory receptor. Thus, our study has demonstrated that purinergic signaling of P2X and P2Y receptors has different effects on olfactory transduction mediated by a defined olfactory receptor and the consequences of purinergic modulation of olfactory activity might depend on stereotypic structures of the odorant-receptor complex.