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鳥類および哺乳類のモデル動物を用いた味覚受容および味覚修飾機構に関する研究

川端, 由子 KAWABATA, Yuko カワバタ, ユウコ 九州大学

2021.03.24

概要

味覚受容機構の基礎的研究として、まず鳥類のモデル動物であるニワトリを用いて脂肪味の受容に関する 研究を行った。ニワトリの口腔組織に機能的な脂肪味受容体G-protein coupled receptor 120 (GPR120)が 存在していること、またニワトリは行動試験において脂肪味を認識できることが報告されていた。しかしな がら、トリグリセリドはGPR120 のような脂肪酸受容体によって認識されるために遊離脂肪酸に消化される 必要があるものの、脂質消化酵素リパーゼの活性がニワトリの口腔組織に存在するかどうかは依然として不 明であった。本研究では、はじめに脂肪味受容体候補遺伝子であるGPR120 およびcluster of differentiation 36 (CD36)に着目し、塩基配列の決定、遺伝子発現解析および受容体機能解析を行った。 ニワトリ口蓋からCD36 をクローニングし、塩基配列を決定した。また、RT-PCR を用いて、GPR120 とCD36 がニワトリ口腔および消化管組織に幅広く発現していることを確認した。さらに、ニワトリGPR120 に作用 する脂肪酸をスクリーニングし、新たに2 種類の脂肪酸でも濃度依存的な活性を示すこと、またこの活性化 はマウスGPR120 アンタゴニストであるAH7614 により濃度依存的に阻害されることを明らかにした。次に、 RT-PCR によって、いくつかのリパーゼ遺伝子が口腔および消化管組織の両方で発現していることを確認した。最後に、リパーゼの基質として蛍光トリグリセリドアナログを用いて口腔組織のリパーゼ活性を解析したと ころ、腺胃や膵臓と同様に口腔組織において機能的なリパーゼが存在することを見出した。

次に、味覚の修飾に起因するような薬剤性味覚障害に関する研究を哺乳類のモデル動物であるマウスを用いて行った。薬剤性味覚障害は生活の質を低下させるが、薬剤が味覚障害を引き起こすメカニズムはまだ解明されていない。本研究では、抗不整脈薬であるフレカイニドの味覚機能への影響を調べた。フレカイニドを単回投与されたマウスは、特に酸味のある味覚物質に対する嗜好性の低下および味覚神経応答の上昇を示した。フレカイニドは、酸味受容体であるマウスOtopetrin 1 (Otop1)を発現するHEK293T細胞のHClに対する応答を増強した。さらに、フレカイニドは味蕾オルガノイドの成長を抑制した。これらの結果は、フレカイニドがマウスOtop1と直接相互作用して、酸味物質に対する味細胞の応答を増強し (短期的効果)、味細胞の成長を阻害する (長期的効果)ことを示唆している。

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