Internalisation of the μ-opioid receptor by endomorphin-1 and leu-enkephalin is dependant on aromatic amino acid residues
- 作者：Mark P. Del Borgo ; Joanne T. Blanchfield ; Istvan Toth
- 关键词：Opioid receptors ; Endomorphin 1 ; Leu-enkephalin ; Receptor internalisation ; Tolerence
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 April 2008
- 卷：16
- 期：8
- 页码：4341-4346
- 文件大小：145 K
摘要
The opioid receptor system in the central nervous system controls a number of physiological processes, most notably pain. However, most opioids currently available have a variety of side-effects as well as exhibiting tolerance. Tolerance is most likely to be a complex phenomenon, however, the role of receptor internalisation is thought to play a crucial role. In this study, we examined the role of aromaticity in ligand-mediated receptor internalisation of the μ-opioid receptor (MOPR). These studies show that the amount of receptor internalisation may be dependant on the amphiphilicity of the ligand. Specifically, deletion of the C-terminus aromatic residues of endomorphin 1, particularly tryptophan reduces receptor-mediated internalisation whilst the addition of tryptophan within the enkephalin sequence increases receptor internalisation and decreases tolerance.