Distinct 5-HT receptors mediate the peristaltic reflex induced by mucosal stimuli in human and guinea pig intestine.
OBJECTIVE
The role of 5-hydroxytryptamine (5-HT) in regulating the peristaltic reflex in humans is unknown. The neural pathways subserving peristalsis induced by mucosal stimulation were characterized in human jejunum and guinea pig colon.


METHODS
Compartmented flat-sheet preparations that enable measurement of 5-HT and sensory transmitter release into one compartment and mechanical responses in adjacent compartments were used.


RESULTS
Mucosal stimuli (2-8 brush strokes) caused concomitant release of 5-HT and calcitonin gene-related peptide (CGRP) into the compartment where stimulation was applied in both species; in contrast, muscle stretch caused release of CGRP only. CGRP release as well as ascending contraction and descending relaxation of circular muscle induced by mucosal stimulation were inhibited by a selective 5-HT4 antagonist in human jejunum and by selective 5-HT4 and 5-HT3 antagonists in guinea pig colon. The effects of the 5-HT3 and 5-HT4 antagonists in guinea pig colon were additive. A selective 5-HT1P antagonist mimicked the effect of the 5-HT4 antagonist. The CGRP antagonist human CGRP8-37 inhibited ascending and descending responses in both species.


CONCLUSIONS
5-HT released by mucosal stimulation initiates a peristaltic reflex by activating 5-HT4/5-HT1P receptors on sensory CGRP neurons in human intestine and 5-HT4/5-HT1P and 5-HT3 receptors in guinea pig colon.
Department of Physiology, Medical College of Virginia, Richmond, USA.
A E
AE
Foxx-Orenstein
J F
JF
Kuemmerle
J R
JR
Grider
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000502:physiology*; D010528:Peristalsis; D011985:Receptors, Serotonin / Q000502:physiology*; D012018:Reflex; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; D015740:Calcitonin Gene-Related Peptide