Morphine induces μ opioid receptor endocytosis in guinea pig enteric neurons following prolonged receptor activation

Abstract

Background & Aims: The μ opioid receptor (μOR) undergoes rapid endocytosis after acute stimulation with opioids and most opiates, but not with morphine. We investigated whether prolonged activation of μOR affects morphine's ability to induce receptor endocytosis in enteric neurons. Methods: We compared the effects of morphine, a poor μOR-internalizing opiate, and (D-Ala2,MePhe4,Gly-ol5) enkephalin (DAMGO), a potent μOR-internalizing agonist, on μOR trafficking in enteric neurons and on the expression of dynamin and β-arrestin immunoreactivity in the ileum of guinea pigs rendered tolerant by chronic administration of morphine. Results: Morphine (100 μmol/L) strongly induced endocytosis of μOR in tolerant but not naive neurons (55.7% ± 9.3% vs 24.2% ± 7.3%; P