The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum.

Contractions to carbachol (0.01–0.3 μM) and to electrical field stimulation (EFS, 0.25–8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally‐mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum.

Atropine (1 μM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3–30 μM), a nicotinic receptor agonist, induced concentration‐dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 μM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum.

In control ileum, histamine (10–100 μM) and the histamine H₁ receptor agonist HTMT (3–10 μM) inhibited the contractions to EFS concentration‐dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H₁ antagonist mepyramine (5–10 μM) but not by the H₂‐ and H₃‐receptor antagonists cimetidine and thioperamide (both 10 μM). In chronically inflamed ileum however, histamine (10–100 μM) and HTMT (3–10 μM) failed to inhibit the contractions to EFS. The histamine H₂ and H₃ receptor agonists dimaprit and R(−)‐α‐methylhistamine did not affect the contractions to EFS in control and inflamed ileum.

The α₂‐receptor agonist UK 14.304 (0.01–0.1 μM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the α₂‐receptor antagonist yohimbine (1 μM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum.

Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H₁ receptors is disturbed during chronic intestinal inflammation whereas the modulation by α₂‐receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.