Influence of 5-HT4 receptor activation on acetylcholine release in human large intestine with endometriosis

Background The 5-HT4 receptor agonist prucalopride enhances large intestinal contractility by facilitating acetylcholine release through activation of 5-HT4 receptors on cholinergic nerves and is effective in patients with constipation. Patients with intestinal endometriosis can present with constipation. We investigated in vitro whether large intestinal endometriotic infiltration influences contractility and facilitation of acetylcholine release by prucalopride. Methods Sigmoid colon or rectum circular muscle strips were obtained at the level of an endometriotic nodule with infiltration of the Auerbach plexus, and at a macroscopically healthy site at least 5 cm cranially from the nodule, in patients undergoing laparoscopic colorectal resection because of symptomatic bowel endometriosis. Responses to muscarinic receptor stimulation and to electrical field stimulation (EFS), and the facilitating effect of prucalopride on acetylcholine release were evaluated. Key results The EC50 and E-max of the contractile responses to the muscarinic receptor agonist carbachol did not differ between healthy and lesioned strips. EFS-induced on-contractions were not different between the healthy and lesioned strips, while the non-nitrergic relaxant responses induced by EFS were decreased in the lesioned strips. The facilitating effect of prucalopride on acetylcholine release in healthy strips was similar to that reported before in macroscopically healthy colon tissue of patients with colon cancer; in lesioned strips, the effect of prucalopride was fully maintained in 6/8 patients and absent in two. Conclusions & inferences Large intestinal endometriosis does not lead to a systematic interference with the cholinergic facilitating effect of prucalopride.