The metabolic evidence of synergistic effect between ohmefentanyl and [D-Pen2, D-Pen5] enkephalin on differentiated SH-SY5Y cells in humans.
Interactions between selective opioid agonists acting at mu- and delta-opioid receptors were evaluated by co-administering a low-effective dose of the selective mu-opioid receptor agonist ohmefentanyl (OMF) with sequentially increasing doses of the selective delta-opioid receptor agonist [D-Pen(2), D-Pen(5)] enkephalin (DPDPE). Microphysiometer was used to measure the extracellular acidification rate (ECAR) of living cells in real-time, which reflected the functional activity after agonist-receptor binding. The synergy (i.e. a more than additive effect) was observed with combinations of these two opioid agonists on differentiated SH-SY5Y cells functionally expressing both mu- and delta-opioid receptors. The demonstration of the synergy suggests that the agonists of the subtypes of opioid receptors can interact at cellular level.
Chen
Z W
ZW
Neuroscience Research Institute, Health Center, Peking University, Xue-Yuan Road 38, 100083, PR, Beijing, China.
Yang
K
K
Wang
Y
Y
Han
J S
JS
D000143:Acids / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D004357:Drug Synergism; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000143:Acids; D000700:Analgesics; D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D004743:Enkephalin, Leucine; C037016:F 7302; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D005283:Fentanyl