The nociceptin (ORL1) receptor: molecular cloning and functional architecture

Nociceptin and the ORL1 receptor share high sequence similarity with opioid peptides, particularly dynorphin A, and their receptors. However, nocicept in and dynorphin A may use distinct molecular pathways to bind and activate their cognate receptors. Activation of the K-opioid receptor by dynorphin A is thought to require interactions of its N-terminal hydrophobic domain ( Y(1)GGF) with the receptor opioid binding pocket, located within the transm embrane helix bundle, while activation of the ORL1 receptor appears to requ ire interactions of the positively charged core (R(8)KSARK) of nociceptin w ith the negatively charged second extracellular receptor loop. (C) 2000 Els evier Science Inc. All rights reserved.