Comparison of the Motor-Stimulating Action of EM523, an Erythromycin Derivative, and Prostaglandin F2 in Conscious Dogs

Abstract

ABSTRACT-The effect of , an erythromycin derivative, on gastrointestinal motility was investigated using conscious dogs in the fasting state, and it was compared with those of motilin and prostaglandin F2a (PGF2a). EM523 and motilin given as i.v. infusions induced strong contractions in the stomach that migrated along the intestine. On the other hand, PGF2a stimulated intestinal contractions, but its effect on gastric motility was weak. EM523 had 1/50 the potency of motilin and 6 times the potency of PGF2a for stimulation of intestinal motility. Atropine at 0.1 mg/kg, i.v. strongly inhibited gastrointestinal contractions induced by EM523 or motilin and partly in hibited PGF2a-induced intestinal motility. ICS-205-930, a 5HT3-receptor antagonist, at a dose of 1 mg/kg, i.v. strongly inhibited EM523 or motilin-induced gastric contractions but did not affect the action of PGF2a. Infusion of EM523 at 100 ttg/kg/hr induced strong migrating contractions even when motility was depress ed by dopamine infusion or laparotomy. Infusion of PGF2a at 300 pg/kg/hr stimulated intestinal but not gastric motility under these conditions. The results of this study indicate that the cholinergic pathway and 5HT3 receptors are involved in EM523 and motilin-induced migrating gastrointestinal contractions, whereas the cholinergic pathway seems to be only partly involved in PGF2a-induced intestinal contractions.

Mitemcinal (GM-611), an orally active motilin receptor agonist, accelerates colonic motility and bowel movement in conscious dogs

“…Similar results in conscious dogs have been demonstrated that low dose motilin (0.2 μg/kg/hr, i. v. infusion) only increased gastric antral motility; more than 5 times higher doses of motilin were required to increase colonic motility in the interdigestive state (Shibata et al, 1995). Inatomi et al (1993) also reported that EM-523, one of the EMA derivatives, administered i. v. infusion at 30 μg/kg/h could induce stronger MMC-like contractions in the gastric antrum, but failed to induce colonic motor activity in conscious dogs. There may be a difference in sensitivity to motilin and motilin receptor agonists between the gastric antrum and the colon in dogs.…”

Erythromycin gastrokinetic activity is partially vagally mediated

“…An alternative, not exclusive to the direct action of erythromycin, is that the central action of erythromycin is not related to erythromycin itself but to another factor. It has been suggested that the final nervous pathway for erythromycin derivative (EM-523) might involve facilitation of serotoninergic transmission (18,31). A similar regulation has also been demonstrated for motilin (20).…”

Gastroprokinetic Effect and Mechanism of SK-896, a New Motilin Analogue, during the Interdigestive Period in Conscious Dogs

“…It has been previously reported [16][17][18] that injection or infusion of motilin (0.1-1.0 Ìg/kg) induced phase III contractile activity in the gastric antrum. Moreover, we reported earlier [4] that SK-896 and human motilin bind the rabbit gastroduodenal motilin receptor with equal ability and that the 50% inhibitory concentrations for binding of 125 I-motilin to this receptor were 3.5 B 1.5 and 3.1 B 1.8 nmol/l, respectively.…”