Species-dependent opioid receptor pharmacology in dogs revealed by binding, signaling, and structural analysis
Year: 2026
Type: preprint
Abstract: Opioid analgesics show variable clinical efficacy across species, whose underlying mechanisms remain insufficiently characterized. Besides pharmacokinetic factors, the present study investigates whether differences in opioid receptor structure and function might contribute to canine-specific opioid pharmacology. Here, we cloned canine µ- (cMOR) and k-opioid receptors (cKOR), expressed them in HEK293 cells, and evaluated ligand binding and ERK1/2 signaling for clinically relevant opioids, comparing results with rat MOR and human KOR. Molecular docking identified conserved and species-specific ligand-receptor interactions. Buprenorphine exhibited high affinity but reduced signaling at canine receptors; morphine showed enhanced µ-selectivity with near-maximal efficacy; butorphanol acted as a full agonist at cKOR but a weak partial agonist at cMOR. These findings demonstrate that opioid receptor sequence variation contributes to species-dependent pharmacodynamics, providing molecular insights relevant to veterinary opioid use and highlighting the value of integrating experimental and computational approaches in comparative pharmacology.
Source: Research Square
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7220469008