Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders
Jesse J. DiCello, Simona Carbone, Ayame Saito, Vi Pham, Agata Szymaszkiewicz, Arisbel B. Gondin, Sadia Alvi, Kiliana Marique, Priyank A. Shenoy, Nicholas A. Veldhuis, Jakub Fichna, Meritxell Canals, Arthur Christopoulos, Céline Valant, Daniel P. Poole
2021American Journal of Physiology-Gastrointestinal and Liver Physiology18 citationsDOIOpen Access PDF
Abstract
This study assesses the use of positive allosteric modulation as a pharmacological approach to enhance opioid receptor signaling in the enteric nervous system. We demonstrate that selective modulation of endogenous delta opioid receptor signaling can suppress colonic motility without causing constipation. We propose that allosteric modulation of opioid receptor signaling may be a therapeutic strategy to normalize gastrointestinal motility in conditions such as irritable bowel syndrome.
Topics & Concepts
Enteric nervous systemMotilityAllosteric regulationAllosteric modulatorOpioidEndogenyReceptorEndogenous opioidDeltaδ-opioid receptorPharmacologyChemistryNeuroscienceBiologyCell biologyBiochemistryPhysicsAstronomyGastrointestinal motility and disordersNeuropeptides and Animal PhysiologyHormonal Regulation and Hypertension