Motilin and erythromycin enhance the in vitro contractile activity of the sphincter of Oddi of the Australian brush-tailed possum.

Erythromycin has been shown to interact with gastrointestinal smooth muscle in a similar manner to motilin, and has been postulated as a motilin receptor agonist. We report that in isolated preparations from the biliary tract of thirty one Australian Brush-tailed Possums (Trichosurus vulpecula) erythromycin acts in a similar manner to motilin. In all muscle strips from the sphincter of Oddi, prepared in both the circular and longitudinal orientation, both synthetic porcine motilin (10(-10) M-10(-6) M) and erythromycin (lactobionate) (10(-8) M-10(-4) M) stimulated contractile activity in a concentration dependent manner, via a direct effect on the smooth muscle (the response was unaffected by tetrodotoxin, omega conotoxin GVIA or atropine). In strips prepared from the gallbladder neither agonist affected the contractile activity in 7 of 8 animals. Motilin was approximately 1000 fold more potent in stimulating contractile activity than erythromycin in both sphincter of Oddi circular strips [pD2 for peak response to motilin 8.67 (mean) +/- 0.06 (SEM) compared with erythromycin 5.67 +/- 0.09] and sphincter of Oddi longitudinal strips [pD2 for peak response to motilin 8.64 (mean) +/- 0.28 (SEM) compared with erythromycin 5.45 +/- 0.23]. The concentration response curves for motilin and erythromycin were similar and both agonists required the presence of extracellular calcium to elicit responses (responses were diminished by verapamil and abolished in calcium free Krebs solution). Our results support the hypothesis that erythromycin mimics the action of motilin in stimulating the sphincter of Oddi in vitro.