title: Chronic activation of ORL1 receptor induces supersensitization of adenylyl cyclase.
abstract: The opioid receptor-like (ORL1) receptor regulates a variety of effectors shared by its close relatives, the opioid receptors. Supersensitization of adenylyl cyclase (AC) is a hallmark of cellular tolerance induced by chronic activation of opioid receptors. To examine if chronic activation of the ORL1 receptor leads to a similar adaptation, a HEK293 cell line stably expressing the human ORL1 receptor (293/ORL1) was established. Chronic treatment of 293/ORL1 cells with nociceptin/OFQ resulted in enhanced AC activity in response to forskolin stimulation. The AC supersensitivity was blocked by pertussis toxin, indicating the involvement of Gi/Go proteins. Likewise, chronic activation of endogenous ORL1 receptors in the neuroblastoma SK-N-SH cells led to Gi/Go-mediated AC supersensitization.
authors.affiliation: Department of Biology and the Biotechnology Research Institute, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon.
authors.forename: R Y
authors.initials: RY
authors.lastname: Chan
authors.forename: Y H
authors.initials: YH
authors.lastname: Wong
mesh_terms: D000262:Adenylyl Cyclases / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists* / Q000096:biosynthesis; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D000262:Adenylyl Cyclases; D000242:Cyclic AMP; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722283:OPRL1 protein, human