PT  - JOURNAL ARTICLE
AU  - Erica S. Levitt
AU  - John T. Williams
TI  - Desensitization and tolerance of mu opioid receptors on pontine Kolliker-Fuse neurons.
AID  - 10.1124/mol.117.109603
DP  - 2017 Jan 01
TA  - Molecular Pharmacology
PG  - mol.117.109603
4099  - http://molpharm.aspetjournals.org/content/early/2017/11/02/mol.117.109603.short
4100  - http://molpharm.aspetjournals.org/content/early/2017/11/02/mol.117.109603.full
AB  - Acute desensitization of mu opioid receptors is thought to be an initial step in the development of tolerance to opioids. Given the resistance of the respiratory system to develop tolerance, desensitization of neurons in the Kölliker-Fuse (KF), a key area in the respiratory circuit, was examined. The activation of G protein-coupled inwardly rectifying potassium (GIRK) current was measured using whole-cell voltage-clamp recordings from KF and locus coeruleus (LC) neurons contained in acute rat brain slices. A saturating concentration of the opioid agonist [Met5]-enkephalin (ME) caused significantly less desensitization in KF neurons compared to LC neurons. In contrast to LC, desensitization in KF neurons was not enhanced by activation of PKC or in slices from morphine-treated rats. Cellular tolerance to ME and morphine was also lacking in KF neurons from morphine-treated rats. The lack of cellular tolerance in KF neurons correlates with the relative lack of tolerance to the respiratory depressant effect of opioids.