IN-VIVO CHARACTERIZATION OF THE COLONIC PROKINETIC EFFECT OF ERYTHROMYCIN IN THE RABBIT

The motor effect of erythromycin was characterized in conscious rabbit s chronically fitted with electrodes and strain-gauge force transducer s implanted along the proximal and distal colon. Fecal pellet output w as also evaluated as an index of propulsive activity. In order to get an insight into the pathways involved in mediating the effect of eryth romycin, the macrolide was also administered after pretreatment with a tropine, nifedipine or ondansetron. Furthermore, in vitro experiments with erythromycin alone and in the presence of atropine, nifedipine, t etrodotoxin or ondansetron were carried out with circular muscle strip s taken from rabbit distal colon. In vivo, erythromycin (0.087-5.6 mg/ kg i.v. bolus) dose-dependently stimulated spike and mechanical activi ties at both colonic levels, with a more marked effect on the distal c olon. Erythromycin also dose-dependently increased the number of abora lly migrating long spike bursts and fecal pellet output. The reproduci bility of the response to erythromycin was confirmed by experiments wi th the dose of 2.8 mg/kg i.v. bolus, repeated in five consecutive expe riments at 48-hour intervals. Nifedipine, but not atropine or ondanset ron, significantly reduced the colonic motor response to erythromycin. In vitro experiments gave results in line with the in vivo data: the concentration-dependent contractile effect of erythromycin was almost suppressed by nifedipine, but resistant to atropine, tetrodotoxin or o ndansetron. In conclusion, this study provides evidence that: (1) eryt hromycin is a prokinetic drug at the colonic level in rabbits, and (2) both in vivo and in vitro, the effects of erythromycin are exerted at the smooth muscle level by mechanisms depending on influx of extracel lular calcium, while muscarinic and 5-HT3 receptors are not involved, at least in this model.