title: Tyr-D-Arg2-Phe-sarcosine4 activates phospholipase C-coupled mu2-opioid receptors in SH-SY5Y cells.
abstract: The dermorphin analogue Tyr-D-Arg2-Phe-sarcosine4 acts as a mu1-opioid receptor agonist, but as a mu2-opioid receptor antagonist, in vivo, yet the biochemical effects of Tyr-D-Arg2-Phe-sarcosine4 are unknown. Therefore, we characterized the effects of Tyr-D-Arg2-Phe-sarcosine4 on the mu-opioid receptor-mediated stimulation of inositol(1,4,5)trisphosphate, and inhibition of cAMP, in SH-SY5Y cells. We report here for the first time that Tyr-D-Arg2-Phe-sarcosine4 has no effect on basal cAMP or inositol(1,4,5)trisphosphate formation, but reversed the effects of fentanyl on these second messengers, consistent with Tyr-D-Arg2-Phe-sarcosine4 acting as a mu2-opioid receptor antagonist, and confirming that the mu-opioid receptors in SH-SY5Y cells are of the mu2 subtype.
authors.affiliation: University Department of Anaesthesia, Leicester Royal Infirmary, UK.
authors.forename: D
authors.initials: D
authors.lastname: Smart
authors.forename: D G
authors.initials: DG
authors.lastname: Lambert
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005283:Fentanyl / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; D015544:Inositol 1,4,5-Trisphosphate; C053418:tyrosyl-arginyl-phenylalanyl-sarcosine; D000242:Cyclic AMP; D010738:Type C Phospholipases; D005283:Fentanyl