Internalisation of the mu-opioid receptor by endomorphin-1 and leu-enkephalin is dependant on aromatic amino acid residues.
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 mu-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.
Del Borgo
Mark P
MP
School of Molecular and Microbial Sciences, University of Queensland, St. Lucia, 4072 Qld, Australia.
Blanchfield
Joanne T
JT
Toth
Istvan
I
D024322:Amino Acids, Aromatic / Q000737:chemistry*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D000242:Cyclic AMP / Q000096:biosynthesis; D004743:Enkephalin, Leucine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization
D024322:Amino Acids, Aromatic; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D004743:Enkephalin, Leucine; D000242:Cyclic AMP