EM574, an erythromycin derivative, is a motilin receptor agonist in the rabbit

This study was performed to examine whether an erythromycin derivative, de( N-methyl)- N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intest...

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Bibliographic Details
Published in:European journal of pharmacology 1997-03, Vol.322 (1), p.63-71
Main Authors: Sato, Fumihiko, Sekiguchi, Masahiro, Marui, Shogo, Inatomi, Nobuhiro, Shino, Akio, Itoh, Zen, Ōmura, Satoshi
Format: Article
Language:English
Subjects:
Animals
Autoradiography
Biological and medical sciences
Digestive system
EM574
Erythromycin
Erythromycin - analogs & derivatives
Erythromycin - pharmacology
Female
Gastrointestinal Agents - pharmacology
Guinea Pigs
In Vitro Techniques
Iodine Radioisotopes
Male
Medical sciences
Motilin
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - metabolism
Pharmacology. Drug treatments
Pyloric Antrum - physiology
Rabbit
Rabbits
Rats
Rats, Sprague-Dawley
Receptor binding
Receptors, Gastrointestinal Hormone - agonists
Receptors, Gastrointestinal Hormone - metabolism
Receptors, Neuropeptide - agonists
Receptors, Neuropeptide - metabolism
Structure-Activity Relationship
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Summary:This study was performed to examine whether an erythromycin derivative, de( N-methyl)- N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (EM574) is a motilin receptor agonist in the rabbit gastrointestinal tract. EM574 and porcine motilin induced contractions in segments of isolated rabbit intestine with pEC 50 values of 8.26±0.04 and 8.69±0.07, respectively, but not in rat or guinea pig preparations. The sensitivity and efficacy of the response to both compounds in rabbits decreased aborally and was insensitive to pretreatment with atropine or tetrodotoxin, but was markedly suppressed under Ca 2+-free conditions. EM574 and porcine motilin specifically displaced [ 125I-Tyr 23]canine motilin bound to gastric antral smooth muscle homogenates with pIC 50 values of 8.21±0.13 and 9.20±0.11, respectively. The pEC 50 value for the contractile response and pIC 50 value for the receptor binding for motilin, EM574, erythromycin A and three other derivatives correlated well ( r=0.94, P
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(96)00983-1