Expression of motilin in the hypothalamus and the effect of central erythromycin on gastric motility in diabetic rats

Abstract

Objective To investigate the expression of motilin-immunoreactive neurons in the hypothalamus and the effect of central administration of erythromycin (EM) on the regulation of gastric motility in diabetic rats. Methods The motilin immunoreactive neurons in the hypothalamus and the hippocampus were detected by immunohistochemistry with rabbit anti-motilin polyclonal antibody. To measure the gastric motility, force transducers were surgically affixed to the gastric serosa. A microinjection syringe was connected via a plastic tube to an injection cannula, which was connected with a stainless steel guide cannula. The syringe was inserted into the right lateral cerebral ventricle for microinjecting the chemicals. Results Diabetic mellitus was successfully induced in cohorts of rats. Motilin-immunoreactive neurons significantly increased in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus in the diabetic rats. Intracerebroventricular (i.c.v.) administration of EM, a motilin receptor agonist, stimulated the gastric motility of diabetic rats. EM (91.56 nmol, i.c.v.) dose-dependently increased the amplitude by (174.82±48.62)% (P < 0.05), and increased the frequency by (70.43±27.11)% (P < 0.05) in 5 min. The stimulatory effect lasted more than 15 min to the end of the measurement, and can be blocked partially by the prior treatment of motilin receptor antagonist GM-109. Conclusion Motilin-immunoreactive neurons are increased in the PVN and SON of the hypothalamus in diabetic rats. Centrally administered EM may regulate gastric motility by binding to the central motilin receptors, and central motilin might be involved in regulation of gastric motility in diabetic rats.

Effect of motilin on gastric distension sensitive neurons in arcuate nucleus and gastric motility in rat

“…It is well established that the Arc represents an important receptive structure for hormonal, metabolic and neuronal signals reflecting the energy status. It was suggested that the hypothalamus was a main target of motilin action 4,5 for GI tract motility. Our present study shows for the first time that neurons in Arc are sensitive to GD.…”

“…It has been recognized that PVN is an important center in energy balance, which receives neural input from the arcuate nucleus and plays a critical role in food intake and energy integration 15 . Neuroanatomy study reveals that neurons in PVN of hypothalamus can project directly to Arc, 16 and motilin positive neurons were observed in PVN 5 . It is questionable whether motilin‐containing neurons in PVN directly project to Arc.…”

“…15 Neuroanatomy study reveals that neurons in PVN of hypothalamus can project directly to Arc, 16 and motilin positive neurons were observed in PVN. 5 It is questionable whether motilin-containing neurons in PVN directly project to Arc. Our retrograde tracing combining with motilin immunohistochemistry staining study showed that FG/motilin labeled neurons existed in PVN by injection of FG in Arc, suggesting that motilin-containing neuron in PVN may directly project their axons to the Arc and perhaps involved in the regulation of GD-sensitive neurons activity in Arc.…”

“…However, motilin and motilin receptors precursor mRNA neither in rat nor in mice have been identified and they exist as pseudogenes. Although rat motilin has not been available, motilin from other mammals such as pig, guinea pig and rabbit has been used in the rat study [1][2][3][4][5]9 and motilin immunoreactivity has been observed in the rat brain. 5,17 In recent years, a series of studies on the effects of motilin in the central nervous system on regulation of GI functions have been performed in our laboratory in animal models of rats.…”

“…In recent years, a series of central nervous effects of motilin on gastrointestinal (GI) activity has been studied. It showed that administration of motilin or erythromycin in the lateral hypothalamus (LH), 4,5 ventral medial hypothalamus (VMH) 6 , and amygdala 7 could significantly enhance gastric motility. Furthermore, lateral ventricle microinjected motilin could change the firing frequency of gastric distention‐related neurons in dorsal vagal complex, 5 LH 4 , and hippocampus 8 .…”