Zubare-Samuelov Meirav, Peri Irena, Tal Michael, Tarshish Mark, Spielman Andrew I, Naim Michael
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, PO Box 12, Rehovot 76-100, Israel.
Am J Physiol Cell Physiol. 2003 Nov;285(5):C1255-62. doi: 10.1152/ajpcell.00149.2003. Epub 2003 Jul 2.
The sweeteners saccharin, D-tryptophan, and neohesperidin dihydrochalcone (NHD) and the bitter tastant cyclo(Leu-Trp) stimulated concentration-dependent pigment aggregation in a Xenopus laevis melanophore cell line similar to melatonin. Like melatonin, these tastants inhibited (by 45-92%) cAMP formation in melanophores; pertussis toxin pretreatment almost completely abolished the tastant-induced cAMP inhibition, suggesting the involvement of the inhibitory pathway (Gi) of adenylyl cyclase. The presence of luzindole (melatonin receptor antagonist) almost completely abolished the inhibition of cAMP formation induced by saccharin, D-tryptophan, and cyclo(Leu-Trp) but only slightly affected the inhibitory effect of NHD. In contrast, the presence of an alpha2-adrenergic receptor antagonist, yohimbine, almost completely abolished the inhibition of cAMP formation induced by NHD but had only a minor effect on that induced by the other tastants. Thus saccharin, D-tryptophan, and cyclo(Leu-Trp) are melatonin receptor agonists whereas NHD is an alpha2-adrenergic receptor agonist, but both pathways lead to the same transduction output and cellular response. Formation of D-myo-inositol 1,4,5-trisphosphate (IP3) in melanophores was reduced (15-58%, no concentration dependence) by saccharin, D-tryptophan, and cyclo(Leu-Trp) stimulation but increased by NHD stimulation. Tastant stimulation did not affect cGMP. Although some of the above tastants were found to be membrane permeant, their direct activation of downstream transduction components in this experimental system is questionable. MT1 and MT2 melatonin receptor mRNAs were identified in rat circumvallate papilla taste buds and nonsensory epithelium, suggesting the occurrence of MT1 and MT2 receptors in these tissues. Melatonin stimulation reduced the cellular content of cAMP in taste cells, which may or may not be related to taste sensation.
甜味剂糖精、D -色氨酸和新橙皮苷二氢查耳酮（NHD）以及苦味剂环（亮氨酸 - 色氨酸）在非洲爪蟾黑素细胞系中刺激浓度依赖性色素聚集，其作用类似于褪黑素。与褪黑素一样，这些味觉剂抑制（45% - 92%）黑素细胞中cAMP的形成；百日咳毒素预处理几乎完全消除了味觉剂诱导的cAMP抑制，表明腺苷酸环化酶的抑制途径（Gi）参与其中。鲁辛朵（褪黑素受体拮抗剂）的存在几乎完全消除了糖精、D -色氨酸和环（亮氨酸 - 色氨酸）诱导的cAMP形成抑制，但仅轻微影响NHD的抑制作用。相反，α2 -肾上腺素能受体拮抗剂育亨宾的存在几乎完全消除了NHD诱导的cAMP形成抑制，但对其他味觉剂诱导的抑制作用影响较小。因此，糖精、D -色氨酸和环（亮氨酸 - 色氨酸）是褪黑素受体激动剂，而NHD是α2 -肾上腺素能受体激动剂，但两条途径都导致相同的转导输出和细胞反应。糖精、D -色氨酸和环（亮氨酸 - 色氨酸）刺激可使黑素细胞中D -肌醇1,4,5 -三磷酸（IP3）的形成减少（15% - 58%，无浓度依赖性），但NHD刺激则使其增加。味觉剂刺激不影响cGMP。尽管发现上述一些味觉剂可透过细胞膜，但在该实验系统中它们对下游转导成分的直接激活存在疑问。在大鼠轮廓乳头味蕾和非感觉上皮中鉴定出MT1和MT2褪黑素受体mRNA，表明这些组织中存在MT1和MT2受体。褪黑素刺激降低了味觉细胞中cAMP的细胞含量，这可能与味觉有关，也可能无关。
