Blocking opioid receptors enhanced delayed stomach contractions from vagus nerve stimulation — kappa agonists (dynorphin-like) were the most effective at suppressing these contractions.
Kappa opioids most effectiveAt suppressing vagus nerve-driven stomach contractions
What the researchers found
Naloxone (100 to 1000 micrograms/kg) did not affect the initial stomach response to vagus nerve stimulation. But it dose-dependently enhanced the delayed response (from vagal afferent fibers). This means endogenous opioids normally restrain the delayed stomach excitation.
Met-enkephalin was markedly more potent than the mu-agonist DAGO and the kappa-agonist dynorphin A(1-13) at inhibiting both types of vagal stomach responses.
The delta-selective agonist DPDPE mimicked met-enkephalin's inhibitory effects. The delta-selective antagonist ICI 174,864 blocked DPDPE's effects. This confirmed delta-opioid receptors mediate the gastric inhibition.
The conclusion: natural opioid peptides (likely enkephalins) tonically restrain vagus nerve-driven stomach excitation through delta receptors.
Why it matters
The vagus nerve is the main communication line between the brain and gut. Finding that enkephalins through delta receptors control vagal gastric responses reveals how the opioid system fine-tunes digestion. This matters for understanding gut motility disorders and opioid-related digestive side effects.
How the study worked
Cats had their vagus nerves stimulated electrically. Stomach contractions were measured as gastric pressure changes. Opioid agonists and antagonists were tested systemically. Delta receptor specificity confirmed with selective agonist (DPDPE) and antagonist (ICI 174,864).
What this study cannot tell us
Tested in cats, not people. Only acute stimulation was studied. The relative contribution of central vs peripheral delta receptors was not separated. Anesthesia likely affected the results.
How to read the evidence
Preliminary animal study in cats with systematic receptor comparison.
When this study was published
Published in 1988 — important for understanding opioid effects on gastric motility.
The bigger picture
The vagus nerve is the main communication line between brain and gut. Understanding how opioid peptides modulate vagal control of the stomach is important for treating functional GI disorders.
Questions still open
- Could selective kappa agonists treat gastroparesis?
- Do endogenous opioids contribute to functional dyspepsia?
Common questions
What is the vagus nerve?
Why do opioids affect the stomach?
Read the original research
Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats.
British journal of pharmacology, 95(2), 329-34
Citation
Okamoto, T; Kurahashi, K; Fujiwara, M. (1988). Effects of naloxone and opioid agonists on gastric excitatory responses to stimulation of the vagus nerve in cats.. British journal of pharmacology, 95(2), 329-34.