Differential alterations in tachykinin NK 2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation

Abstract

Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are intestinal disorders which disrupt normal colonic motility. Enteric tachykinins are well-recognised to play a role in the motor control of the gut, and increased colonic levels of substance P are seen in IBD, whereas decreased levels have been reported in ICC. In this investigation, we have characterised the tachykinin receptor population of normal human colonic circular smooth muscle and examined any changes that occur in IBD and ICC. The selective tachykinin NK 2 receptor agonist, [β-Ala 8]neurokinin A(4-10), caused concentration-dependent contractions in healthy tissues; neither NK 1 receptor-selective nor NK 3 receptor-selective agonists were contractile. In diseased preparations also, only [β-Ala 8]neurokinin A(4-10) caused contractions with EC 50 values similar to health. The maximum contractile responses ( E max), however, were significantly decreased in both forms of IBD but significantly increased in ICC. The muscarinic acetylcholine receptor agonist, carbachol, also caused contractions in diseased tissues, but EC 50 and E max values were not significantly different from health. The differential changes in contractility found in IBD and ICC are specific to NK 2 receptors, and may reflect the altered levels of substance P or other tachykinins found in these intestinal disorders.