-
- 吉田 有輝
- 東京理科大・院薬
-
- 高橋 英希
- 国立がん研・がん患者病態生理 北里大・薬・生命薬化学
-
- 小野 晴香
- 国立がん研・がん患者病態生理 北里大・薬・生命薬化学
-
- 目黒 由行
- 国立がん研・がん患者病態生理 自治医科大・消化器・一般移植外科
-
- 宮野 加奈子
- 国立がん研・がん患者病態生理
-
- 野中 美希
- 国立がん研・がん患者病態生理
-
- 平山 重人
- 国立がん研・がん患者病態生理 北里大・薬・生命薬化学
-
- 水口 貴章
- 北里大・薬・生命薬化学
-
- 小林 正樹
- 東京理科大・院薬
-
- 田川 亮真
- 東京理科大・院薬
-
- 藤井 秀明
- 北里大・薬・生命薬化学
-
- 樋上 賀一
- 東京理科大・院薬
-
- 上園 保仁
- 国立がん研・がん患者病態生理 国立がん研・先端医療開発セ・支持療法開発 国立がん研・中央病院・支持療法開発
書誌事項
- タイトル別名
-
- Analysis of oxytocin as a positive allosteric modulator(PAM)of the opioid δ- and κ-receptors.
抄録
<p>Oxytocin (OT), composed of nine amino acids, has a wide range of physiological functions such as uterine contractions, maternal/social behavior and anti-stress effects. Recently, it has been reported that OT released from parvocellular neurons alleviates pain. Analgesic effects of OT might be involved in the μ- and κ-opioid receptors (OR) in the rats because it was partially inhibited by the antagonists of μ- and κ-ORs but not δ-ORs. However, it has not been elucidated the mechanism in detail. While we previously reported that OT could enhance the μ-OR activity as a positive allosteric modulator (PAM), it remains unclear whether OT behaves as a PAM for the δ- and κ-OR. We therefore analyzed activities of δ- and κ-OR stimulated by OT in two types of HEK293 cells stably expressing δ- and κ-OR, respectively. For the measurement, we used the CellKeyTM assay system that measures changes of impedance following OR activation. In the assay, OT failed to exert agonistic effects on the δ- and κ-OR, whereas it enhanced the κ-OR activity induced by κ-OR agonists dynorphin A, U50488 and morphine. Interestingly, OT at 10-6 M had no effect on the δ-OR activity induced by δ-OR agonists Leu- and Met-enkephalin, SNC80 and morphine. We also revealed all amino acids of OT except Leu in the position 8 could be involved in PAM activity at the κ-OR. In addition, our competitive receptor-binding analysis disclosed that OT had no effect on the κ-OR orthosteric binding sites. Hence, OT could function as a κ-OR PAM in addition to a μ-OR PAM.</p>
収録刊行物
-
- 日本薬理学会年会要旨集
-
日本薬理学会年会要旨集 93 (0), 2-P-236-, 2020
公益社団法人 日本薬理学会
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1390002184883114112
-
- NII論文ID
- 130007811727
-
- ISSN
- 24354953
-
- 本文言語コード
- ja
-
- データソース種別
-
- JaLC
- Crossref
- CiNii Articles
-
- 抄録ライセンスフラグ
- 使用不可