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NEUROREGULATION AND MOTILITY
1Department of Internal Medicine and Public Health, University of L'Aquila, 67100 L'Aquila; and 2Department of Physiological and Pharmacological Sciences, University of Pavia, 27100 Pavia, Italy
Submitted 24 September 2002 ; accepted in final form 18 March 2003
In the gastrointestinal tract, tachykinin NK1 receptors are
widely distributed in a number of neuronal and nonneuronal cells involved in
the control of gut motor activity. In particular, in the rabbit isolated
distal colon, which is a suitable model system to investigate the contribution
of tachykinins as noncholinergic excitatory transmitters, the influence of
NK1 receptors in the regulation of peristalsis is not known. The
selective NK1-receptor antagonists SR-140333 (0.3 and 1 nM) and
MEN-10930 (0.310 nM) significantly enhanced the velocity of rabbit
colonic propulsion to submaximal stimulation. The prokinetic effect of
SR-140333 was prevented by
N
-nitro-L-arginine (L-NNA), a
nitric oxide synthase inhibitor, indicating that NK1 receptors
located on nitrergic innervation exert a functional inhibitory restraint on
the circular muscle and probably on descending excitatory and inhibitory
pathways during propulsion. Conversely, the selective NK1-receptor
agonist septide (310 nM) significantly inhibited colonic propulsion. In
the presence of L-NNA, the inhibitory effect of septide was
reverted into a prokinetic effect, which is probably mediated by the
activation of postjunctional excitatory NK1 receptors.
myenteric neurons; excitatory pathways; inhibitory pathways
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