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The motilin antagonist ANQ-11125 blocks motilide-induced contractions in vitro in the rabbit.

Abstract：

:Studies on the physiological role of motilin, and more recently, on the relationship between motilin and erythromycin A, have been hampered by the lack of antagonists. We now have discovered such a compound. ANQ-11125 displaces motilin bound to an homogenate of rabbit antral smooth muscle tissue. The dissociation constant (pKd) was 8.16 +/- 0.10. However, ANQ-11125 did not induce contractions of segments of rabbit duodenum, except at high concentrations. In the presence of 1 microM ANQ-11125 the dose response curves of erythromycin-A, De(N-methyl)-N-ethyl-8,9 anhydroerythromycin A 6,9-hemiacetal and motilin were shifted about one log unit to the right, but the responses to ACh and Substance P were unaffected. Schild-analysis showed the competitive nature of the interaction and allowed the calculation of the pA2: 7.03 +/- 0.05 (motilin curves) and 7.55 +/- 0.06 (EM-523 curves). This is the first report of a motilin antagonist. Its properties definitively prove that motilides are motilin agonists.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Peeters TL,Depoortere I,Macielag MJ,Dharanipragada R,Marvin MS,Florance JR,Galdes A

doi

10.1006/bbrc.1994.1060

subject

Has Abstract

pub_date

1994-01-28 00:00:00

pages

411-6

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(84)71060-6

journal_volume

198

pub_type

杂志文章

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