Regulation of colonic propulsion by enteric excitatory and
inhibitory neurotransmitters.
Foxx-Orenstein, A. E., and J. R. Grider.
Departments of Medicine and Physiology, Medical College of
Virginia, Richmond, Virginia 23298-0711
APStracts 3:0055G, 1996.
The contribution of excitatory and inhibitory motor neurotransmitters
to colonic propulsion was examined in isolated segments of guinea pig
colon. Synthetic fecal pellets were inserted at the proximal end of
the segment and the velocity of pellet propulsion across a fixed
distance was measured in the presence and absence of selective
neurotransmitter antagonists. Control velocity (0.97+/-0.02 mm/s) was
inhibited in a concentration-dependent fashion by atropine and the
NK-2a antagonist, MEN-10,376 (IC50 1[mu]M; maximal inhibition 98+/
-1%). The NK-1 antagonist, GR-82,334 (10 [mu]M) also inhibited
velocity by 65+/-9%, consistent with involvement of acetylcholine,
NKA (NK-2 agonist) and SP (NK-1 agonist) in the contractile
components of the peristaltic reflex. Velocity was also inhibited in
a concentration-dependent fashion by the NOS inhibitor, L-NNA (IC50 1
[mu]M; maximal inhibition 96+/-2%), and by the VIP antagonist, VIP10
-28 (IC50 30 nM; maximal inhibition 64+/-6%) consistent with
involvement of both NO and VIP in descending relaxation of circular
muscle and contraction of longitudinal muscle. A combination of
threshold concentrations of L-NNA and the NK-2a antagonist was
synergistic (53+/-7% inhibition). The potentiation implied that the
ascending and descending phases were functionally coupled in series.
We conclude that blockade of neurotransmitters that mediate either
phase of the peristaltic reflex inhibits colonic propulsive activity.
Serial coupling of the phases leads to synergism between inhibitors,
a condition of potential therapeutic importance.
Received 18 September 1995; accepted in final form 26 February
1996.
APS Manuscript Number G414-5.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 March 96