Abstract
The present study demonstrates a conditional, agonist-dependent phosphorylation of the max-opioid receptor (MOR-1) by cyclic AMP-dependent protein kinase (PKA) in membrane preparations of MOR-l-transfected neuroblastoma Neuro2A cells. Opioid agonist-dependent phosphorylation occurs in a time- and concentration-dependent manner (EC50 ~40 nM) and can be abolished by the receptor antagonist naloxone. Stoichiometric analysis indicates incorporation of a maximum of 6 mol of phosphate/mol of receptor in the presence of 1 μM morphine and 6 nM PKA. Although morphine and related alkaloids as well as some peptide agonists (PLO17 and β-endorphin) stimulated phosphorylation of MOR-1 by PKA, the potent μ-opioid-selective peptide [D-Ala2,N-MePhe4, Gly-ol5]-enkephalin (DAMGO) or other enkephalin analogues such as [D-Ala2]-Met5-enkephalinamide (DALA), [D-Ala2,D-Leu5]- enkephalin (DADLE), and Met5-enkephalin had no effect. The lack of the effect of DAMGO on MOR-1 phosphorylation state was evident also after chronic pretreatment. These results suggest the existence of different agonist- dependent conformations of MOR-1. Furthermore, phosphorylation may be a useful parameter with which to identify different agonist-receptor conformations.
Original language | English (US) |
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Pages (from-to) | 231-239 |
Number of pages | 9 |
Journal | Journal of Neurochemistry |
Volume | 71 |
Issue number | 1 |
DOIs | |
State | Published - Jul 1998 |
Keywords
- Cyclic AMP-dependent protein kinase
- Morphine
- Opioid
- Phosphorylation
- [D-Ala, N-MePheGly-ol]- enkephalin
- μ-Opioid receptor