Erythromycin Central Motilin Role And Its Induction Paraventricular Nucleus C-fos Protein Expression

Motilin, a 22-amino acid residue gastrointestinal peptide, is released by the endocrine cells in the mucosa of the upper part of the small intestine. The peripheral function of motilin mainly involved the regulation of the migrating motor complex (MMC)-phase Ⅲ of the gastrointestinal tract in interdigestive state. Early more than twenty years ago, the motilin-like immunoreactivity was found in the central nervous system (CNS), and the following studies and researches indicated that motilin may have various central effects, including the regulation of feeding and drinking behaviour, central and brainstem neuronal modulation, pituitary hormone secretion, and reducing the levels of anxiety in mice. In recent years our laboratory focused on the effect of motilin on the gastric motility in rats and its mechanism. We have already observed that microinjection of motilin in several regions of the brain can stimulate gastric motor activity in conscious rats. Erythromycin (EM) is a generally accepted peripheral motilin receptor agonist, but it is still unknown whether EM also has a motilin-like effect in CNS.Objective: To study whether EM has a motilin-like effect in CNS and its possible mechanism.Materials and Methods: (1) Recording of gastric motility in conscious rats: Guide cannulas were implanted unilaterally in the lateral cerebroventricle of fasted rat brain. The gastric motility was recorded by a force transducer sewn on the gastric antrum. After I.C.V. microinjection of EM9.16nmol, 45.78nmol, 91.56nmol, and EM91.56nmol+GM109 2.95nmol, the changes in the gastric motility were recorded. In the control group, the rats were I.C.V. injected with the same volume NS.(2) C-Fos protein immunohistochemistry test: fasted Wistar rats were implanted with guide cannulas in lateral cerebroventricle. After adaptation of rats to the lab conditions for 2 weeks, the expression of c-Fos protein in the brain was checked by means of immunohistochemistry 90 minutes after the injection of EM45.78nmol, or 91.56nmol, or EM91.56nmol+GM109 2.95nmol, or NS of the same volume into the lateral cerebroventricle.Results:(1) A dose-dependent motility-stimulating effect of EM on the gastric motor amplitude in conscious rats was observed, which lasts for 10 minutes in the EM50 group, and for 20 minutes in the EM91.56nmol group. GM109 2.95nmol can partially blocked the stimulating effect of EM91.56nmol on the gastric motor amplitude. There were no statistically significant differences in gastric motility between EM9.16nmol group and control group. No changes in gastric motor frequency was observed.in all group.(2) I.C.V. injection of EM45.78nmol or EM91.56nmol can dose-dependently induce the expression of c-Fos protein in PVN. GM109 2.95nmol can partially block the effect EM91.56nmol on c-Fos expression in PVN.Conclusion:(1) I.C.V. injection of EM has a motility-stimulating effect on gastric motor amplitude in conscious rats, which might be mediated by the central motilin receptor.(2) I.C.V. injection of EM induces the expression of c-Fos protein in PVN, which indicates that one of the possible regions where EM exerts its motilin-like effect is PVN.