Idiopathic chronic constipation: tachykinins as cotransmitters in colonic contraction

• Published in: European journal of clinical investigation Vol. 31; no. 4; pp. 349 - 355
• Main Authors: Mitolo-Chieppa, D., Mansi, G., Nacci, C., De Salvia, M. A., Montagnani, M., Potenza, M. A., Rinaldi, R., Lerro, G., Siro-Brigiani, G., Mitolo, C. I., Rinaldi, M., Altomare, D. F., Memeo, V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.04.2001; Blackwell; Blackwell Publishing Ltd
• Subjects: Adult; Aged; Biological and medical sciences; Chronic Disease; Colon - innervation; Colon - physiopathology; Constipation - metabolism; Constipation - physiopathology; Electric Stimulation; Gastroenterology. Liver. Pancreas. Abdomen; Human colonic circular muscle; Humans; idiopathic chronic constipation; In Vitro Techniques; Medical sciences; Middle Aged; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth - drug effects; Muscle, Smooth - innervation; Muscle, Smooth - physiopathology; Neurotransmitter Agents - pharmacology; Neurotransmitter Agents - physiology; off-contraction; Other diseases. Semiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; tachykinins; Tachykinins - pharmacology; Tachykinins - physiology; Human; Pharmacologic test; Agonist; Pathophysiology; Pathogenesis; Contractility; Idiopathic; Exploration; Biological activity; Chronic; Digestive diseases; Intestinal disease; Constipation; Tachykinin; Biological receptor
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1046/j.1365-2362.2001.00810.x

Background Tachykinins (TKs) have been shown to be involved in the excitatory enteric motor pathway. This study aimed to examine the direct and nerve‐mediated effect of specific NK1, NK2 and NK3 receptor agonists and antagonists in colonic preparations from control subjects and patients with idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of Sar9Met(O2)11 substance P (selective NK1 receptor agonist), [Ala5,β‐Ala8]‐neurokinin A (4–10) (selective NK2 receptor agonist) and [MePhe7]‐neurokinin B (selective NK3 receptor agonist) were tested on colonic circular muscle strips to evaluate the direct drug effects. In addition, in the presence of atropine, the role of TKs in the off‐contraction that follows the typical inhibitory response evoked by low frequencies of electrical field stimulation (0·5–10 Hz, 20 V, 1 ms pulse trains lasting 1 min) was investigated. Results In control preparations, the rank order of potency was: NK2 receptor‐selective agonist > NK3 receptor‐selective agonist > NK1 receptor‐selective agonist. The off‐contraction was found to be reduced by about 30–40% in colonic circular muscle from ICC patients with respect to controls. Incubation with the NK1 receptor agonist did not modify the off‐contraction measurements in either control or ICC preparations. Conversely, both NK2 and NK3 receptor agonists significantly (P < 0·01) increased the off‐contraction in ICC preparations only. This increased response was fully antagonized by MEN‐10627, a NK2 and NK3 receptor antagonist depending on the dose. Conclusions We may conclude that ICC is hyporesponsive to TKs and that the contractile reflex to distension is greatly reduced in ICC disease, but can be restored by incubation with NK2 and NK3 receptor agonists.