Involvement of 5‐HT3 and 5‐HT4 receptors in colonic motor patterns in rats

E-ISSN： 1365-2982|27|7|914-928

ISSN： 1350-1925

Source： NEUROGASTROENTEROLOGY & MOTILITY (ELECTRONIC), Vol.27, Iss.7, 2015-07, pp. : 914-928

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Abstract

AbstractBackgroundColonic migrating motor complexes in the rat constitute two distinct propulsive motor patterns, pan‐colonic rhythmic long distance contractions (LDCs), and rhythmic propulsive motor complexes (RPMCs) occurring primarily in the mid/distal colon. Interstitial cells of Cajal govern their rhythmicity, but their occurrence is dependent on neural programs. Our aim was to investigate the involvement of 5‐HT3 and 5‐HT4 receptors in the generation and pharmacological control of the motor patterns.MethodsEffects of 5‐HT‐related drugs on colonic motor patterns were analyzed through spatio‐temporal maps created from video recordings of whole organ motility.Key Results5‐HT3 antagonists abolished RPMCs and LDCs. 5‐HT4 agonists inhibited LDCs; they promoted RPMCs, which was blocked by the 5‐HT4 antagonist GR 125487. 5‐HT and the 5‐HT3 agonist m‐CPBG strongly inhibited LDCs and RPMCs.Conclusions & InferencesThe generation of LDCs involves ongoing 5‐HT release acting on 5‐HT3 and 5‐HT4 receptors. The spontaneous generation of RPMCs involves ongoing 5‐HT release acting on 5‐HT3 but not 5‐HT4 receptors. Prucalopride and mosapride promote RPMCs, an effect that is inhibited by the 5‐HT4 receptor antagonist GR 125487. A 5‐HT3 agonist does not promote RPMCs. Segmentation, including a pattern of sequential segmental activity not previously described, can occur without significant involvement of 5‐HT3 and 5‐HT4 receptors. 5‐HT and a 5‐HT3 agonist are strongly inhibitory indicating that 5‐HT receptors are present in inhibitory pathways which are normally not involved in the generation of spontaneous or distention‐induced motor patterns.