Abstract
We have investigated sensitization of reflexes in the isolated rat colon in order
to develop a model that might prove useful for investigating how the sensitivity of
enteric reflexes can be altered by prior stimulation. Records were taken of circular
muscle tension, 7–10 mm oral and anal to radial distension exerted by a hook passed
through the wall of the colon. A test stimulus of 1.5 g produced consistent contractions
both oral and anal to the distension. A conditioning protocol, consisting of repeated
application of 3 g for 30 s with 30 s between the stimuli for 30 min, doubled the
amplitudes of reflex contractions that were evoked by the test stimuli but did not
change the sensitivity of the muscle to the direct action of carbachol. The enhanced
responses persisted for at least 40 min. The enhancement of reflexes was not reduced
by antagonists of tachykinin NK3 receptors or of 5-HT3 receptors, but the reflex oral to stimulation was reduced by NK1 and NK3 antagonists added together. Sensitization was abolished by the cyclo-oxygenase and
thromboxane synthase inhibitor, indomethacin. We conclude that sensitization can be
reliably induced in vitro and that the model described in the present work can be
used to investigate drugs that interfere with the sensitization process.
Keywords
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Article info
Publication history
Accepted:
December 17,
2001
Received in revised form:
November 20,
2001
Received:
June 15,
2001
Identification
Copyright
© 2002 Elsevier Science B.V. Published by Elsevier Inc. All rights reserved.
