The metabolic evidence of synergistic effect between ohmefentanyl and [D-Pen(2), D-Pen(5)] enkephalin on differentiated SH-SY5Y cells in humans

Interactions between selective opioid agonists acting at mu- and delta -opi oid receptors were evaluated by co-administering a low-effective dose of th e selective mu -opioid receptor agonist ohmefentanyl (OMF) with sequentiall y increasing doses of the selective delta -opioid receptor agonist [D-Pen(2 ), D-Pen(5)] enkephalin (DPDPE). Microphysiometer was used to measure the e xtracellular acidification rate (ECAR) of living cells in real-time, which reflected the functional activity after agonist-receptor binding. The syner gy (i.e. a more than additive effect) was observed with combinations of the se two opioid agonists on differentiated SH-SY5Y cells functionally express ing 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. (C) 2001 Elsevier Science Ireland Ltd. All rights reser ved.