Paradoxical effects of opioids in suppression of colonic motility.

Opioid receptor agonists reduce spontaneous nitrergic motor inputs in mouse distal colon, increasing phasic contractions, with effects abolished by tetrodotoxin, L-NNA, or apamin.

• Why it matters: Opioids slow colonic transit and cause constipation, but the cellular mechanism—especially whether they suppress excitatory or inhibitory motor pathways—remains incompletely defined.
• What they did: In mouse colon, spontaneous enteric nitrergic inputs were measured and tested against tetrodotoxin, L-NNA, or apamin; EM-1 was used to probe MOR effects, alongside Ca2+ transients in interstitial cells of Cajal and membrane potentials in circular muscle.
• The result: MOR, DOR, and KOR agonists suppressed anterogradely propagating neurogenic contractions and EM-1 enhanced Ca2+ transients and depolarized circular muscle, consistent with suppression of tonic inhibition and impaired poststimulus depolarization and peristaltic contractions.

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