Opioid agonists binding and responses in SH-SY5Y cells

Abstract

SH-SY5Y (human neuroblastoma) cultured cells, known to have μ-opioid receptors, have been used to assess and compare the ability of eight representative μ-selective compounds from diverse opioid families to recognize and activate these receptors. A wide range of receptor affinities spanning a factor of 10,000 was found between the highest affinity fentanyl analogs (K i = 0.1nM) and the lowest affinity analog, meperidine (K i = 1 μM ). A similar range was found for inhibition of PGE 1-stimulated cAMP accumulation with a rank order of activities that closely paralleled binding affinities. Maximum inhibition of cAMP accumulation by each compound was about 80%. Maximum stimulation of GTPase activity (∼50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that μ-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of μ-agonists functional responses.