AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 6 879-G886, Copyright © 1989 by American Physiological Society
Tissue origin of peptide-responsive eicosanoid production in rabbit intestine
L. E. Leduc and R. D. Zipser
Division of Gastroenterology/Department of Medicine, Harbor-University of California, Los Angeles, Torrance 90509.
Different layers of rabbit large and small intestine display different
peptide sensitivity and different profiles of eicosanoid release. Isolated
perfused mesenteric pedicle alone, with muscularis/submucosa or with
muscularis and mucosa from normal small bowel, normal colon, or inflamed
colon were stimulated with bradykinin (BK) or
n-formyl-methionyl-leucyl-phenylalanine (fMLP). Released prostaglandin
(PG)E2, thromboxane (Tx)B2, and leukotriene (LT)B4 were assayed using
extensively validated radioimmunoassays. In rabbit colon, PGE2 arises
primarily from the mesentery, while in small intestine the
muscularis/mucosa releases 70-80% of the total PGE2. BK releases no
significant thromboxane from healthy colon, although both
muscularis/submucosa and mucosa respond in inflamed colon. In contrast,
fMLP stimulates thromboxane from muscularis/submucosa and mucosa of even
healthy colon, while release is greatly potentiated in inflammation.
Lipoxygenase in the colon is regulated differently than cyclooxygenase; it
is not stimulated by BK in either healthy or inflamed colon. fMLP releases
equal amounts of LTB4 from healthy and inflamed colon, but release was
primarily from healthy colonic mucosa, whereas it was distributed
throughout mesenteric pedicle, muscularis, and mucosa in inflamed colon.
The ability of normal colonic mucosa to release proinflammatory LTB4 in
response to a chemotactic factor (fMLP) produced by enteric bacteria
suggests a possible role for these compounds as a stimulus for inflammation
in some patients with inflammatory bowel disease.
