Agonist-dependent development of delta opioid receptor tolerance in the colon
Jesse J DiCello, Ayame Saito, Pradeep Rajasekhar, Benjamin W Sebastian, Rachel M McQuade, Arisbel B Gondin, Nicholas A Veldhuis, Meritxell Canals, Simona E Carbone, Daniel P Poole
Cellular and Molecular Life Sciences | SPRINGER BASEL AG | Published : 2019
The use of opioid analgesics is severely limited due to the development of intractable constipation, mediated through activation of mu opioid receptors (MOR) expressed by enteric neurons. The related delta opioid receptor (DOR) is an emerging therapeutic target for chronic pain, depression and anxiety. Whether DOR agonists also promote sustained inhibition of colonic transit is unknown. This study examined acute and chronic tolerance to SNC80 and ARM390, which were full and partial DOR agonists in neural pathways controlling colonic motility, respectively. Excitatory pathways developed acute and chronic tolerance to SNC80, whereas only chronic tolerance developed in inhibitory pathways. Both..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) Australia
National Health and Medical Research Council (NHMRC) Australia 1049730 and 1121029 (DPP & MC), 1083480 (DPP); JJD, AB and PR are supported by NHMRC Australian Postgraduate Awards. Research in DPP's laboratory is funded in part by Takeda Pharmaceuticals. The research presented in this manuscript was not related to this agreement.