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Effects of erythromycin on human colonic circular muscle in idiopathic chronic constipation
Author(s) -
D. Mitolo Chieppa,
G. Mansi,
Rosanna Rinaldi,
M Serio,
Carmela Nacci,
Monica Montagnani,
Maria Assunta Potenza,
Maria Antonietta De Salvia,
C. I. Mitolo,
Marcella Rinaldi,
D. F. Altomare
Publication year - 2000
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2000.00589.x
Subject(s) - motilin , contraction (grammar) , erythromycin , muscle contraction , endocrinology , medicine , stimulation , motility , chemistry , isometric exercise , receptor , muscle relaxation , enteric nervous system , pharmacology , biology , biochemistry , antibiotics , genetics
Background Erythromycin has been shown to have profound prokinetic effects on the gastrointestinal tract of humans and animals, probably through its action on endogenous motilin receptors. The purpose of this study was to determine both the direct and indirect effects (‘off contraction’) of erythromycin and motilin on ex vivo circular muscle strips of the distal colon from patients with or without idiopathic chronic constipation (ICC). Materials and methods Cumulative concentrations of erythromycin (1–20 μM) and motilin (0.05–1 μM) were tested in both control and ICC preparations in order to evaluate the direct drugs effect. A range doses of both erythromycin (0.5–10 μM) and motilin (0.05–0.5 μM) were tested on their ability to affect the off‐contraction that follows the typical inhibitory response evoked by low frequencies of Electrical Field Stimulation (EFS) (1–5 Hz, 20 V, 1 msec pulse trains lasting 1 min). Results The direct effect of both erythromycin and motilin was a slight increase (less than 10% of the maximal ACh‐induced contraction) in the basal tension, with no dose–response relationship. The off‐contraction, evoked by EFS, was not affected by drugs pretreament in control preparations. Conversely, in ICC preparations both drugs significantly increased the off‐contraction (about 30%). Conclusions Erythromycin causes mainly an indirect contractile effect in circular muscle strips from ICC patients. This effect may be related to the activation of inhibitory neuronal motilin receptors. This activation might potentiate NANC relaxation, proportionally increasing the circumferential reflex contraction that follows the EFS‐induced relaxation.