Premium
ERYTHROMYCIN DERIVATIVES ABT 229 AND GM 611 ACT ON MOTILIN RECEPTORS IN THE RABBIT DUODENUM
Author(s) -
Clark Mj,
Wright T,
Bertrand Pp,
Bornstein Jc,
Jenkinson Km,
Verlinden M,
Furness Jb
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.1440-1681.1999.03022.x
Subject(s) - motilin , agonist , medicine , chemistry , partial agonist , endocrinology , muscarinic acetylcholine receptor , pharmacology , erythromycin , receptor , biology , biochemistry , antibiotics
1. The present study was undertaken to determine whether the macrolide antibiotic erythromycin, its stable motilide derivatives ABT 229 and GM 611 and motilin act at the same receptors on intestinal muscle 2. Each compound contracted the longitudinal muscle of the rabbit duodenum in a concentration‐dependent manner that was unaffected by 1 μmol/L tetrodotoxin. The potency order (pEC 50 values in brackets) was motilin (8.4), ABT 229 (7.6), GM 611 (7.5) and erythromycin (6.0). 3. The motilin receptor antagonists GM 109 and [phe 3 ,leu 13 ]motilin, both shifted the concentration–response curves for each agonist to the right, but did not affect concentration–response relationships for the muscarinic agonist carbachol. Schild regression analysis yielded similar pA 2 values for GM 109 (in the range 7.2–7.5) for all agonists. This analysis was not done for [phe 3 ,leu 13 ]motilin, which was a non‐competitive antagonist and partial agonist. 4. It is concluded that erythromycin, the motilides and motilin act at the same (motilin) receptor on rabbit duodenal muscle and do not have any detectable actions at other receptors in this preparation.