Morphine leads to contraction of the ileal circular muscle via inhibition of the nitrergic pathway in mice

Hiroki Iwata, Shizuko Tsuchiya, Tomonori Nakamura, Shingo Yano

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Morphine inhibits small intestinal transit in mice, although few μ-opioid receptors are present in the ileum. The present study focused on the action of morphine in the isolated mouse ileum to reveal the mechanism by which morphine inhibits mouse small intestinal transit. In the isolated circular muscle, morphine caused tonic contraction. This contraction was potently inhibited by naloxone and the μ-opioid receptor antagonist cyprodime. Moreover, the response was almost completely inhibited by tetrodotoxin and NG-nitro-l-arginine, but only moderately inhibited by atropine and indomethacin. In the isolated longitudinal muscle, morphine caused no or only slight contractions. Furthermore, electrically induced contraction was dose-dependently depressed by morphine, an effect that was not reversed by naloxone. These findings indicate that 1) morphine-induced circular muscle contraction occurs in the mouse ileum, 2) the contraction occurs through μ-opioid receptors mainly by inhibiting the release of nitric oxide from nitrergic nerves, although cholinergic nerves are at least partly involved in this contractile mechanism, and 3) inhibition of descending relaxation of peristalsis by morphine may slow small intestinal transit.

Original languageEnglish
Pages (from-to)66-70
Number of pages5
JournalEuropean journal of pharmacology
Issue number1
Publication statusPublished - 2007 Nov 21
Externally publishedYes


  • Circular muscle contraction
  • Morphine
  • Mouse ileum
  • Nitric oxide
  • Opioid receptor

ASJC Scopus subject areas

  • Pharmacology


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