AJP - Gastrointestinal and Liver Physiology, Vol 252, Issue 3 293-G300, Copyright © 1987 by American Physiological Society
Site and mechanisms of action of kinins in rat ileal mucosa
G. Warhurst, M. Lees, N. B. Higgs and L. A. Turnberg
Kinin-induced secretion in the intestine is accompanied by marked increases
in mucosal adenosine 3', 5'-cyclic monophosphate (cAMP) and prostanoids
that undoubtedly contribute to the overall secretory response. The cellular
site at which these effects are initiated is unclear although a recent
hypothesis has suggested the epithelial cell as the target for kinin action
(6). We have investigated the effects of kallidin on the
phospholipase-prostanoid-cAMP pathway in whole ileal mucosa and in
epithelial cells isolated from the same tissue in the rat. Kallidin (1
microM) stimulated a marked rise (24 to 30-fold) in PG (prostaglandin) E2
release from the serosal surface of stripped ileal mucosa within 1-2 min,
which correlated closely with the rise in mucosal short-circuit current.
Mucosal cAMP levels were also increased two to threefold by kallidin.
However, kinins were unable to elicit effects under the same conditions in
suspensions of viable epithelial cells. PGE2 release was unaffected by
kallidin or bradykinin at concentrations up to 100 microM, whereas cAMP
levels could be stimulated by forskolin and PGE2 but not by kinin. Studies
of intestinal phospholipase A2 (PLA2) activity also suggest a nonepithelial
site for kinin action. This enzyme is responsible for liberating
arachidonic acid from cellular phospholipids and has been shown to be
activated by kinins in several tissues. In the intestine, PLA2 activity was
found to be concentrated within the subepithelium with significantly lower
levels in the epithelium itself. In addition, kallidin was unable to
influence phospholipid labeling (an indirect measure of PLA2 activity) in
cells incubated with [14C]arachidonic acid.(ABSTRACT TRUNCATED AT 250
WORDS)
