AJP - Gastrointestinal and Liver Physiology, Vol 259, Issue 5 753-G759, Copyright © 1990 by American Physiological Society
Leukotriene D4 excitation of rabbit distal colon arises in the region of the muscularis mucosae
W. H. Percy, S. Y. Lee, M. B. Burton, T. Tolentino and R. Burakoff
Division of Gastroenterology, Winthrop-University Hospital, Mineola 11501.
We previously have demonstrated in vivo that intra-arterial administration
of leukotriene D4 (LTD4) causes increased myoelectric and mechanical
activity in the rabbit distal colon. The aim of this study was to use both
in vivo and in vitro techniques to try to elucidate the mechanism
underlying this effect. In vivo the excitatory response of the rabbit
distal colon to LTD4 was abolished by pretreatment with atropine (0.1 mg/kg
iv) or hexamethonium (5 mg/kg iv) or the LTD4 receptor antagonist SK&F
102922 (0.8 micrograms/kg ia). In vitro neither the longitudinal nor the
circular muscle layer responded to LTD4 (10(-10) to 10(-7) M) with a
contractile response. Over the same concentration range, LTD4 caused
contractions of the muscularis mucosae that were attenuated by either
SK&F 102922 (10(-9) to 10(-7) M) or indomethacin (10(-6) M) but were
unaffected by atropine (10(-6) M), pyrilamine (10(-6) M), or tetrodotoxin
(10(-6) M). Full thickness segments of longitudinal muscle, circular
muscle, and muscularis mucosae did not contract to LTD4. These data imply
that LTD4-induced excitation of the rabbit distal colon in vivo arises as a
result of the excitation of LTD4 receptors in the region of the muscularis
mucosae and that this leads ultimately to the release of acetylcholine onto
the muscularis propria. It is proposed that one possible mechanism leading
to the latter effect is an increased excitability of intrinsic nerves
resulting from a prostaglandin-induced depression of norepinephrine release
from nerves impinging on the submucosal plexus.
