Premium
The first and third intracellular loops together with the carboxy terminal tail of the δ‐opioid receptor contribute toward functional interaction with Gα 16
Author(s) -
Chan Anthony S. L.,
Law Ping Y.,
Loh Horace H.,
Ho Peter N. N.,
Wu WaiMan,
Chan Joy S. C.,
Wong Yung H.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02040.x
Subject(s) - opioid receptor , receptor , microbiology and biotechnology , opioid , adenylyl cyclase , enzyme linked receptor , g protein , enkephalin , opioid peptide , 5 ht5a receptor , phospholipase c , intracellular , transmembrane domain , chemistry , biology , biochemistry
Opioid peptides exert their regulatory effects on both central and pheripheral nervous systems via multiple opioid receptors that are linked to seemingly identical sets of guanine nucleotide‐binding regulatory proteins (G proteins). In contrast to the μ‐opioid receptor, the δ‐opioid receptor can efficiently stimulate phospholipase C via G 16 . We used a series of μ/δ‐opioid receptor chimeras to examine the involvement of intracellular receptor domains in the recognition of G 16 . After ascertaining that the chimeras can bind opioid ligands with high affinity and elicit inhibition of adenylyl cyclase, COS‐7 cells were cotransfected with cDNAs encoding Gα 16 and a μ/δ‐opioid receptor chimera and assayed for [ d ‐Ala 2 , d ‐Leu 5 ]enkephalin‐induced stimulation of phospholipase C. Our results indicate that (i) the carboxy terminal tail of the δ‐opioid receptor is necessary but insufficient for conferring coupling to Gα 16 , (ii) the third inner loop together with the carboxy terminal tail of the δ‐opioid receptor can provide sufficient contact domains for Gα 16 , and (iii) the first inner loop of the δ‐opioid receptor, in particular Leu 80 , as well as the fifth transmembrane domain and/or the third extracellular loop may also contribute in defining the fidelity of interaction between the δ‐opioid receptor and Gα 16 . These results indicate that efficient coupling of the δ‐opioid receptor to Gα 16 requires the participation of most of the intracellular regions, including the first intracellular loop.