Olfactory GPCRs (ORs) in mammalian olfactory receptor neurons (ORNs) mediate excitation through the Gα_s family member Gα_olf. Here we tentatively associate a second G protein, Gα_o, with inhibitory signaling in mammalian olfactory transduction by first showing that odor evoked phosphoinositide 3-kinase (PI3K)-dependent inhibition of signal transduction is absent in the native ORNs of mice carrying a conditional OMP-Cre based knockout of Gα_o. We then identify an OR from native rat ORNs that are activated by octanol through cyclic nucleotide signaling and inhibited by citral in a PI3K-dependent manner. We show that the OR activates cyclic nucleotide signaling and PI3K signaling in a manner that reflects its functionality in native ORNs. Our findings lay the groundwork to explore the interesting possibility that ORs can interact with two different G proteins in a functionally identified, ligand-dependent manner to mediate opponent signaling in mature mammalian ORNs.

哺乳动物嗅觉受体神经元 (ORN) 中的嗅觉 GPCR (OR) 通过 Gα _s家族成员 Gα _olf介导兴奋。在这里，我们初步将第二种 G 蛋白 Gα _o与哺乳动物嗅觉转导中的抑制信号传导联系起来，首先表明在携带条件性 OMP 的小鼠的天然 ORN 中不存在气味诱发的磷酸肌醇 3-激酶 (PI3K) 依赖性信号转导抑制。 -基于 Cre 的 Gα _o敲除. 然后，我们从天然大鼠 ORN 中鉴定出一个 OR，这些 ORN 通过环核苷酸信号被辛醇激活，并被柠檬醛以 PI3K 依赖性方式抑制。我们表明 OR 以反映其在天然 ORN 中的功能的方式激活环核苷酸信号传导和 PI3K 信号传导。我们的研究结果为探索 OR 可以以功能鉴定的配体依赖性方式与两种不同的 G 蛋白相互作用以介导成熟哺乳动物 ORN 中的对手信号传导的有趣可能性奠定了基础。