title: 5-HT released by mucosal stimuli initiates peristalsis by activating 5-HT4/5-HT1p receptors on sensory CGRP neurons.
abstract: The intestinal peristaltic reflex can be elicited by mucosal stimulation or circular muscle stretch. Muscle stretch activates extrinsic, whereas mucosal stimulation activates intrinsic calcitonin gene-related peptide (CGRP)-containing sensory neurons. The present study examined the role of 5-hydroxytryptamine (5-HT) in sensory transmission. A three-compartment preparation of rat colon was used that enables separate measurement of sensory transmitters and modulators. Mucosal stimuli (2-8 brush strokes) caused concurrent increase in 5-HT and CGRP release in proportion to the intensity of stimulation. Release of both 5-HT and CGRP occurred exclusively into the central compartment where the stimuli were applied. Exogenous 5-HT caused a concentration-dependent release of CGRP. Release of CGRP induced by exogenous 5-HT or mucosal stimulation was inhibited by selective 5-HT4 and 5-HT1p antagonists but was not affected by 5-HT1A, 5-HT2, and 5-HT3 antagonists. Ascending contraction and descending relaxation of circular muscle measured in the peripheral orad and caudad compartments, respectively, were also selectively inhibited by 5-HT4 and 5-HT1p antagonists added to the central but not peripheral compartments. In contrast, muscle stretch elicited CGRP but not 5-HT release; the ascending contraction and descending relaxation components of the peristaltic reflex induced by muscle stretch were not affected by 5-HT antagonists. We conclude that 5-HT released by mucosal stimulation initiates the peristaltic reflex by activating 5-HT4/5-HT1p receptors on sensory CGRP-containing neurons.
authors.affiliation: Department of Physiology, Medical College of Virginia, Richmond 23298, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Grider
authors.forename: J F
authors.initials: JF
authors.lastname: Kuemmerle
authors.forename: J G
authors.initials: JG
authors.lastname: Jin
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003106:Colon; D007413:Intestinal Mucosa / Q000187:drug effects / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism*; D010528:Peristalsis / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D011985:Receptors, Serotonin / Q000502:physiology*; D012018:Reflex / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D015740:Calcitonin Gene-Related Peptide