The gastrointestinal motor stimulating activity of erythromycin (EM) was studied in conscious dogs. It was found that a 20-min intravenous infusion of EM lactobionate at a dose of 50-100 micrograms (potency) X kg-1 X h-1 induced a group of strong contractions in the stomach and the duodenum, and the contractions migrated along the small intestine to the terminal ileum. The EM-induced contractions were quite similar to the naturally occurring interdigestive migrating contractions (IMC) in the gastrointestinal tract in frequency, contractile force, and duration of the contractions, migrating velocity, and accompanying peaks of plasma motilin concentration. The EM-induced contractions in the stomach were inhibited by feeding and intravenous infusion of pentagastrin (1.5 micrograms X kg-1 X h-1) but were not affected by secretin; these findings are identical to those found with the naturally occurring and motilin-induced contractions. Like motilin, EM stimulated motor activity only during the interdigestive state. We conclude that EM induces IMC associated with the release of endogenous motilin in the dog.

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To elucidate the molecular mechanisms underlying the development of diabetic neuropathy, we isolated the Schwann cells from the sciatic nerves of adult rats and characterized the polyol pathway activity. Despite the presence of aldose reductase (AR) activity, no accumulation of sorbitol was observed in the cells cultured under 30 mM glucose conditions. Increased levels of sorbitol were detected in the medium conditioned by these cells. SNK-860 (fidarestat), an inhibitor of AR, decreased the sorbitol levels at 10(-6)M, while addition of SDI-158, an inhibitor of sorbitol dehydrogenase, did not affect the level in the cells grown in high glucose. These observations suggested that sorbitol produced by AR in the isolated Schwann cells may be predominantly excreted. In contrast, a significant increase in sorbitol level was observed in cells cultured under hyperosmotic conditions with 30 mM glucose. A significant correlation was observed between sorbitol level and AR activity (r = 0.998). The increase was suppressed by addition of SNK-860, while SDI-158 augmented sorbitol accumulation in a dose-dependent manner. These results suggested that the isolated Schwann cells may not accumulate sorbitol unless the activity of AR is augmented by some as yet undetermined mechanism under high glucose conditions, such as the hyperosmotic stress induced in this study.

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