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

Abstract

Colonic 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. Effects of 5-HT-related drugs on colonic motor patterns were analyzed through spatio-temporal maps created from video recordings of whole organ motility. 5-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. The 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.