Differential alterations in tachykinin NK2 receptors in isolated colonic circular smooth muscle in inflammatory bowel disease and idiopathic chronic constipation
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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
NK2 receptor agonist, [beta-Ala8]neurokinin A(4-10), caused concentration-dependent
contractions in healthy tissues; neither NK1 receptor-selective nor NK3 receptor-selective
agonists were contractile. In diseased preparations also, only [beta-Ala8]neurokinin
A(4-10) caused contractions with EC50 values similar to health. The maximum contractile
responses (Emax), 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 EC50 and Emax values were not significantly
different from health. The differential changes in contractility found in IBD and
ICC are specific to NK2 receptors, and may reflect the altered levels of substance
P or other tachykinins found in these intestinal disorders.