A CYCLIC-NUCLEOTIDE-SUPPRESSIBLE CONDUCTANCE ACTIVATED BY TRANSDUCIN IN TASTE CELLS

A CYCLIC-NUCLEOTIDE-SUPPRESSIBLE CONDUCTANCE ACTIVATED BY TRANSDUCIN IN TASTE CELLS
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DOI:
10.1038/376085a0
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发表时间:
1995-07-06
期刊:
影响因子:
64.8
通讯作者:
MARGOLSKEE, RF
MARGOLSKEE, RF
中科院分区:
综合性期刊1区
文献类型:
--
作者:
KOLESNIKOV, SS;MARGOLSKEE, RF

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味可分为四种主要感觉:咸、酸、甜、苦、咸和酸是通过心尖通道直接传递的(1-4),而甜和苦则利用环核苷酸第二信使(5-11)。我们已经证明,杆状转导蛋白存在于哺乳动物的味觉感受器细胞中,在那里它被苦味受体激活,进而激活磷酸二酯酶(12)。在这里,我们将来自转导蛋白的磷酸二酯酶相互作用区的多肽引入青蛙味觉细胞,这些多肽在部分细胞中引起向内的全细胞电流,我们发现这些多肽的作用被IBMX和Forsklin可逆地抑制,这表明转导蛋白激活的磷酸二酯酶。环核苷酸抑制整个细胞电流,表明环核苷酸可能调节味觉细胞的电导。IBMX改变味觉细胞对两种味觉刺激的反应,暗示磷酸二酯酶参与味觉转导。亚微摩尔的环核苷酸直接抑制来自味觉细胞质膜的由内向外的斑块的电导,而不依赖于蛋白质的磷酸化。通道的不同寻常之处在于它们被环核苷酸抑制,而不是被环核苷酸激活,我们认为转导蛋白通过磷酸二酯酶降低环核苷酸水平,激活环核苷酸可抑制的电导,导致钙离子内流和味觉细胞去极化。
TASTE can be divided into four primary sensations: salty, sour, sweet and bitter, Salty and sour are directly transduced by apical channels(1-4), whereas sweet and bitter utilize cyclic nucleotide second messengers(5-11). We have shown that rod transducin is present in mammalian taste receptor cells, where it is activated by a bitter receptor and in turn activates a phosphodiesterase(12). Here we introduce into frog taste cells peptides derived from transducin's phosphodiesterase-interaction region, which cause an inward whole-cell current in a subset of cells, We find that the peptides' effects are reversibly suppressed by IBMX and forskolin, indicative of a transducin-activated phosphodiesterase. Cyclic nucleotides suppress the whole-cell current, indicating that cyclic nucleotides may regulate taste-cell conductance. IBMX modifies taste-cell responses to two taste stimuli, implicating phosphodiesterase in taste transduction. Submicromolar cyclic nucleotides directly suppress the conductance of inside-out patches derived from the taste-cell plasma membrane, independently of protein phosphorylation. The channels are unusual in that they are suppressed, rather than activated by cyclic nucleotides, We propose that transducin, via phosphodiesterase, decreases cyclic nucleotide levels to activate the cyclic-nucleotide-suppressible conductance, leading to Ca2+ influx and taste-cell depolarization.