Boehning Darren, Moon Cheil, Sharma Sumit, Hurt K Joseph, Hester Lynda D, Ronnett Gabriele V, Shugar David, Snyder Solomon H
Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Neuron. 2003 Sep 25;40(1):129-37. doi: 10.1016/s0896-6273(03)00596-8.
Carbon monoxide (CO) is a putative gaseous neurotransmitter that lacks vesicular storage and must be synthesized rapidly following neuronal depolarization. We show that the biosynthetic enzyme for CO, heme oxygenase-2 (HO2), is activated during neuronal stimulation by phosphorylation by CK2 (formerly casein kinase 2). Phorbol ester treatment of hippocampal cultures results in the phosphorylation and activation of HO2 by CK2, implicating protein kinase C (PKC) in CK2 stimulation. Odorant treatment of olfactory receptor neurons augments HO2 phosphorylation and activity as well as cyclic guanosine monophosphate (cGMP) levels, with all of these effects selectively blocked by CK2 inhibitors. Likewise, CO-mediated nonadrenergic, noncholinergic (NANC) relaxation of the internal anal sphincter requires CK2 activity. Our findings provide a molecular mechanism for the rapid neuronal activation of CO biosynthesis, as required for a gaseous neurotransmitter.
一氧化碳（CO）是一种假定的气态神经递质，它缺乏囊泡储存，并且必须在神经元去极化后迅速合成。我们发现，CO的生物合成酶血红素加氧酶-2（HO2）在神经元刺激过程中被CK2（以前称为酪蛋白激酶2）磷酸化而激活。用佛波酯处理海马培养物会导致CK2使HO2磷酸化并激活，这表明蛋白激酶C（PKC）参与了CK2的刺激作用。用气味剂处理嗅觉受体神经元会增加HO2的磷酸化和活性以及环磷酸鸟苷（cGMP）水平，而所有这些效应均被CK2抑制剂选择性阻断。同样，CO介导的肛门内括约肌非肾上腺素能、非胆碱能（NANC）舒张需要CK2的活性。我们的研究结果为气态神经递质所需的CO生物合成的快速神经元激活提供了一种分子机制。
