Abnormal Tph-5-HT-SR4 signalling has been found in diverticular disease,50 inflammatory bowel disease51 and irritable bowel syndrome.52 Previous observations have shown increased Tph1 activity, EC cell 5-HT content and 5-HT release, but not decreased sert activity in patients with chronic constipation.11,53,54 In agreement, our results confirmed that aged colon exhibited an activated Tph-5-HT-SR4 signalling pathway with a decreased sert expression. Here, HTR5A is linked to irritable bowel syndrome.