TY - JOUR T1 - Gα<sub>L1</sub> (Gα<sub>14</sub>) Couples the Opioid Receptor-Like<sub>1</sub> Receptor to Stimulation of Phospholipase C JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 232 LP - 238 VL - 288 IS - 1 AU - Lisa Y. Yung AU - Sushma A. Joshi AU - Robbie Y.K. Chan AU - Joy S.C. Chan AU - Gang Pei AU - Yung H. Wong Y1 - 1999/01/01 UR - http://jpet.aspetjournals.org/content/288/1/232.abstract N2 - In most tissues and cells the opioid receptor-like (ORL1) receptor regulates effectors primarily through the pertussis toxin (PTX)-sensitive guanine nucleotide-binding regulatory proteins (G proteins) Gi/Go. Many Gi-coupled receptors possess additional capability to interact with one or more PTX-insensitive G proteins. Using the βγ-induced stimulation of type 2 adenylyl cyclase as a readout, we screened the ability of ORL1 receptor to interact with a panel of PTX-insensitive G proteins. In the presence of PTX, activation of the ORL1 receptor resulted in the stimulation of type 2 adenylyl cyclase only in HEK 293 cells coexpressing the α subunit of Gz, G12, G14, or G16, but not in cells coexpressing G11, G13, or Gq. Coupling to both Gz and G16 was expected because close relatives of the ORL1 receptor, the opioid receptors, are known to couple productively to these G proteins. ORL1 receptor coupling to either G12 or G14 has not been demonstrated. As predicted by the type 2 adenylyl cyclase assays, activation of the ORL1 receptor resulted in the formation of inositol phosphates in COS-7 cells transiently cotransfected with Gα14. The ORL1receptor-mediated stimulation of phospholipase C was found to be Gα14 dependent, agonist dose dependent, ligand selective, and PTX insensitive. We conclude that G14 can link the ORL1 receptor to regulation of phopholipase C. The American Society for Pharmacology and Experimental Therapeutics ER -