1. CHOLINERGIC and TACHYKININERGIC NEUROTRANSMISSION IN ADULT TRANSVERSE and SIGMOID COLONIC CIRCULAR MUSCLE
- Author
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M. P. Stanton, John M. Hutson, James L. Keck, Bridget R. Southwell, and Joel C. Bornstein
- Subjects
medicine.medical_specialty ,Carbachol ,Contraction (grammar) ,Hepatology ,business.industry ,Gastroenterology ,Sigmoid colon ,digestive system diseases ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Muscarinic acetylcholine receptor ,medicine ,Tetrodotoxin ,Cholinergic ,Neurokinin A ,business ,Acetylcholine ,medicine.drug - Abstract
Aim There have recently been reports of reduced tachykinin (TK) levels in the colonic circular muscle (CCM) in both children and adults with slow-transit constipation (STC), suggesting a relationship between TK deficiency and impaired colonic motility. In this study, we have examined the role of TKs and acetylcholine in mediating contraction in the adult colon, in order to determine the relative importance of these excitatory neurotransmitters. Methods Isotonic contractile responses to carbachol (cholinomimetic, 10 μm), NKA (neurokinin A receptor agonist, 100 nmol) and electrical field stimulation (EFS) were measured, in transverse (n = 5) and sigmoid (n = 7) colon. EFS was repeated in hyoscine (2 μm); NK1, NK2 and NK3 receptor antagonists (SR 140333, SR 48968, SR 142801, 200 μm); and NOLA (NOS inhibitor, 100 μm). Responses were re-tested with tetrodotoxin (TTX, 1 mm). Results Carbachol and NKA dose-dependently induced contractions in all specimens. The maximal NKA induced contraction was similar to the maximal carbachol contraction in sigmoid colon, but only 1/4 of the maximal carbachol contraction in transverse colon. EFS alone elicited similar responses in the sigmoid and the transverse CCM (40 and 32% of the maximal carbachol response, respectively). Hyoscine reduced the contractile response to EFS by 2/3 in sigmoid CCM, and by 1/2 in transverse CCM. NOLA caused a small increase in EFS-induced contraction in both sigmoid and transverse CCM. Individually, the TK antagonists did not produce significant changes in contractile responses elicited by EFS. However, when incubated together, the three TK antagonists produced a large reduction in EFS-induced contraction, by 1/4–3/4 in sigmoid, and by 1/4 in transverse CCM. EFS-induced responses were abolished in TTX, suggesting that responses were neuro-neuronal. Conclusion There is both a muscarinic cholinergic and tachykininergic input to contraction in the human colon. Muscarinic input produces at least 1/2 of EFS-induced contraction. Tachykinins produce at least 1/4 of the contraction in response to EFS in transverse colon. Tachykinins have an even greater input to EFS-induced contraction in the sigmoid colon.
- Published
- 2001
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