Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of 125I-motilin to duodenal muscle.
Erythromycin, one of the macrolide antibiotics, and its derivatives had been found to mimic actions of exogenous motilin, a gastrointestinal peptide hormone. We found that some of the macrolide compounds inhibited the specific binding of 125I-motilin to rabbit duodenum muscle at 15 C in a dose-dependent fashion. The inhibitory activity of several macrolides examined did not relate to their antibacterial activity but to their motilin-like activity. A 50% inhibition by EM536, a non-antibacterial erythromycin derivative with the highest motilin-like activity, was obtained at 3-40 nM and little higher than that of non-radioactive motilin (5-6 nM) under the present conditions. The results suggest that erythromycin and its derivatives mimic physiological actions of motilin by acting as agonists for a motilin receptor.
Kondo
Y
Y
Department of Physical Biochemistry, College of Medical Technology, Gunma University, Maebashi, Japan.
Torii
K
K
Itoh
Z
Z
Omura
S
S
D000818:Animals; D004386:Duodenum / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D009037:Motilin / Q000378:metabolism / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism; D011817:Rabbits; D011964:Receptors, Gastrointestinal Hormone / Q000187:drug effects / Q000378:metabolism*; D018013:Receptors, Neuropeptide; D013329:Structure-Activity Relationship
D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; D004917:Erythromycin