Editing Morphine (section)

=== Constipation ===
Like [[loperamide]] and other opioids, morphine acts on the [[myenteric plexus]] in the intestinal tract, reducing gut motility, and causing constipation. The gastrointestinal effects of morphine are mediated primarily by [[mu Opioid receptor|μ-opioid receptors]] in the bowel. By inhibiting gastric emptying and reducing propulsive [[peristalsis]] of the intestine, morphine decreases the rate of intestinal transit. Reduction in gut secretion and increased intestinal fluid absorption also contribute to the constipating effect. Opioids also may act on the gut indirectly through tonic gut spasms after inhibition of [[nitric oxide]] generation.<ref name="pmid15082884">{{cite journal | vauthors = Stefano GB, Zhu W, Cadet P, Bilfinger TV, Mantione K | title = Morphine enhances nitric oxide release in the mammalian gastrointestinal tract via the micro(3) opiate receptor subtype: a hormonal role for endogenous morphine | journal = Journal of Physiology and Pharmacology | volume = 55 | issue = 1 Pt 2 | pages = 279–88 | date = March 2004 | pmid = 15082884 }}</ref> This effect was shown in animals when a nitric oxide precursor, [[L-arginine]], reversed morphine-induced changes in gut motility.<ref name="Calignano, Moncada and Di Rosa">{{cite journal | vauthors = Calignano A, Moncada S, Di Rosa M | title = Endogenous nitric oxide modulates morphine-induced constipation | journal = Biochemical and Biophysical Research Communications | volume = 181 | issue = 2 | pages = 889–93 | date = December 1991 | pmid = 1755865 | doi = 10.1016/0006-291X(91)91274-G }}</ref>