title: Opioid agonists binding and responses in SH-SY5Y cells.
abstract: SH-SY5Y (human neuroblastoma) cultured cells, known to have mu-opioid receptors, have been used to assess and compare the ability of eight representative mu-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 (Ki = 0.1nM) and the lowest affinity analog, meperidine (Ki = 1 microM). A similar range was found for inhibition of PGE1-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 (approximately 50%) was also similar for all compounds except the lowest affinity meperidine. Both effects were naloxone reversible. These results provide further evidence that mu-receptors are coupled to inhibition of adenylate cyclase and that the SH-SY5Y cell line is a good system for assessment of mu-agonists functional responses.
authors.affiliation: Molecular Research Institute, Palo Alto, CA 94304.
authors.forename: E M
authors.initials: EM
authors.lastname: Costa
authors.forename: B B
authors.initials: BB
authors.lastname: Hoffmann
authors.forename: G H
authors.initials: GH
authors.lastname: Loew
mesh_terms: D000527:Alprostadil / Q000494:pharmacology; D000700:Analgesics / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism / Q000494:pharmacology; D005283:Fentanyl / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008614:Meperidine / Q000378:metabolism / Q000494:pharmacology; D009019:Morphinans / Q000378:metabolism / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000378:metabolism* / Q000494:pharmacology; D010111:Oxymorphone / Q000378:metabolism / Q000494:pharmacology; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D014407:Tumor Cells, Cultured
chemical_list: D000700:Analgesics; D004723:Endorphins; D004745:Enkephalins; D009019:Morphinans; D009294:Narcotics; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; C058443:4-methoxymethylfentanyl; C044708:morphiceptin, N-Me-Phe(3)-; D008614:Meperidine; D010111:Oxymorphone; D000242:Cyclic AMP; D020558:GTP Phosphohydrolases; D000527:Alprostadil; C017114:carfentanil; D005283:Fentanyl; C047238:metazocine