Positive allosteric modulation of endogenous delta opioid receptor signaling in the enteric nervous system is a potential treatment for gastrointestinal motility disorders

Author:

DiCello Jesse J.123,Carbone Simona E.13ORCID,Saito Ayame1,Pham Vi1,Szymaszkiewicz Agata4,Gondin Arisbel B.13,Alvi Sadia1,Marique Kiliana1,Shenoy Priyank13,Veldhuis Nicholas A.13,Fichna Jakub4,Canals Meritxell56,Christopoulos Arthur1,Valant Celine1,Poole Daniel P.13ORCID

Affiliation:

1. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

2. Department of Physiology, Monash University Biomedicine Discovery Institute, Clayton, Victoria, Australia

3. Australian Research Council Centre of Excellence in Convergent Bio-Nano Science and Technology, Parkville, Victoria, Australia

4. Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland

5. Division of Physiology, Pharmacology and Neuroscience, Queen’s Medical Centre, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom

6. Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, The Midlands, United Kingdom

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.

Funder

Medical University of Lodz

Department of Health, Australian Government | National Health and Medical Research Council

Australian Research Council

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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