AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 6 947-G954, Copyright © 1990 by American Physiological Society
Chemotactic peptide effects on intestinal electrolyte transport
T. A. Barrett, M. W. Musch and E. B. Chang
Department of Medicine, University of Chicago, Illinois 60637.
The bacterial-derived chemotactic peptide
N-formylmethionyl-leucyl-phenylalanine (fMLP) increases short-circuit
current (Isc) and arachidonic acid metabolism (AAM) in rabbit ileum and
distal colon. Serosal (s) or mucosal (m) addition of fMLP transiently
increases Isc. Half-maximally effective dose and maximal increases in Isc
were 32 nM and 84 microA/cm2 in ileum and 234 nM and 80 microA/cm2 in
colon, respectively. Piroxicam, a cyclooxygenase inhibitor, diminished the
Isc response by 97% in colon and 69% in ileum. Changes in Isc were
dependent on Cl- and HCO3- in the bathing media. In ileum, fMLP inhibited
m-to-s 36Cl- fluxes and stimulated s-to-m 36Cl- fluxes. These changes in
Cl- flux were also inhibited by piroxicam. fMLP stimulated prostaglandin E2
(PGE2) release in intact tissue and in isolated subepithelial components.
Increased tissue adenosine 3',5'-cyclic monophosphate levels were detected
in intact tissue but not in isolated components. Previous desensitization
of ileum to PGE1 inhibited fMLP stimulation of Isc in ileum by 88%.
Desensitization to fMLP in ileum failed to alter the effect of PGE1 (10
microM) on Isc. In isolated microsomal membranes of ileal enterocytes, fMLP
binding sites could not be demonstrated, suggesting that fMLPs action was
initially mediated via stimulation of nonepithelial cell cyclooxygenase
activity. The above results indicate that fMLP stimulates net secretion in
both ileum and colon probably by the activation of AAM.
