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AN ACTION OF ERYTHROMYCIN IN THE INTESTINE THAT IS NOT MEDIATED VIA MOTILIN RECEPTORS
Author(s) -
Furness JB,
Clark MJ,
Wright T,
Bertrand PP,
Bornstein JC,
Verlinden M
Publication year - 1999
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.1999.03002.x
Subject(s) - motilin , erythromycin , endocrinology , medicine , receptor , ileum , guinea pig , chemistry , jejunum , muscle contraction , biology , pharmacology , biochemistry , antibiotics
1. Erythromycin lactobionate caused a concentration‐ dependent inhibition of nerve‐mediated contractions of the longitudinal muscle of the guinea‐pig ileum, with a threshold for effect of 10–30 μmol/L. The non‐antibiotic derivative of erythromycin ABT‐229 had a similar effect, but was approximately 10‐fold less potent. At a greater concentration (1 mmol/L), erythromycin also depressed the direct contractile effect of 10 μmol/L carbachol on the muscle. 2. Human/porcine motilin (up to 100 μmol/L) did not reduce the nerve‐mediated contractions, although it did contract the muscle (threshold 30 μmol/L). Antagonists of motilin receptors (phe 3 leu 13 motilin, up to 1 μmol/L, and GM‐109, up to 3 μmol/L) did not reduce responses to erythromycin. 3. Erythromycin contracted the longitudinal muscle of the rabbit duodenum, with a threshold concentration of 0.1 μmol/L and ABT‐229 contracted this tissue at a threshold concentration of 0.01 μmol/L. Effects of both agonists were antagonized by the motilin receptor antagonists phe 3 leu 13 motilin (0.3 μmol/L) and GM‐109 (1 μmol/L). 4. It is concluded that the site(s) at which erythromycin acts in the guinea‐pig ileum is not a motilin receptor and that ABT‐229 is selective for the motilin receptor in comparison with non‐motilin erythromycin sites and is unlikely to act at the latter site in therapeutic doses.