Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP3-odors"
Blocking adenylyl cyclase inhibits olfactory generator currents induced by "IP3-odors"
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DOI：
10.1152/jn.2000.84.1.575
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发表时间：
2000-07-01
影响因子：
2.5
通讯作者：
Zufall, F
中科院分区：
文献类型：
--
作者：
Chen, S;Lane, AP;Zufall, F
脊椎动物嗅觉受体神经元 (ORN) 通过腺苷酸环化酶/cAMP 第二信使级联将气味刺激转变成电信号，但这种 cAMP 级联是否介导所有气味或仅介导某些气味类别的转导仍存在广泛争论。为了解决这个问题，我们分析了由气味引起的发电机电流，这些电流在之前的生化测定中未能产生 cAMP，而是产生了 IP3（“IP3-气味”）。我们发现，在单个蝾螈 ORN 中，对“cAMP 气味”和 IP3 气味的感觉反应并不相互排斥，而是在同一细胞中共存。 IP3 气味诱导的电流表现出与 cAMP 气味或直接激活 cAMP 级联诱导的电流相同的生物物理特性。通过使用腺苷酸环化酶的两种有效拮抗剂 SQ22536 和 MDL12330A 破坏腺苷酸环化酶以阻止 cAMP 形成，我们表明该分子步骤对于两种气味类别的转导都是必要的。为了评估这些结果是否也适用于哺乳动物，我们通过记录场电位来检查完整小鼠主嗅上皮 (MOE) 对 IP3 气味的电生理反应。结果表明，即使在检查对 IP3 气味高度敏感的“热点”时，腺苷酸环化酶的抑制也能阻止小鼠 MOE 对两种气味类别的 EOG 反应。
Vertebrate olfactory receptor neurons (ORNs) transduce odor stimuli into electrical signals by means of an adenylyl cyclase/cAMP second messenger cascade, but it remains widely debated whether this cAMP cascade mediates transduction for all odorants or only certain odor classes. To address this problem, we have analyzed the generator currents induced by odors that failed to produce cAMP in previous biochemical assays but instead produced IP3 ("IP3-odors"). We show that in single salamander ORNs, sensory responses to "cAMP-odors" and IP3-odors are not mutually exclusive but coexist in the same cells. The currents induced by IP3-odors exhibit identical biophysical properties as those induced by cAMP odors or direct activation of the cAMP cascade. By disrupting adenylyl cyclase to block cAMP formation using two potent antagonists of adenylyl cyclase, SQ22536 and MDL12330A, we show that this molecular step is necessary for the transduction of both odor classes. To assess whether these results are also applicable to mammals, we examine the electrophysiological responses to IP3-odors in intact mouse main olfactory epithelium (MOE) by recording field potentials. The results show that inhibition of adenylyl cyclase prevents EOG responses to both odor classes in mouse MOE, even when "hot spots" with heightened sensitivity to IP3-odors are examined.