Effects Of α-MSH On Glucose-sensing And Gastric Distension Sensitive Neurons In Rat Dorsal Vagal Complex

Background:α-melanocyte-stimulating hormone(α-MSH) is processed from pro-opiomelanocortin(POMC) and acts on the melanocortin receptors MC3 and MC4. Intracerebroventricular(ICV) administration ofα-MSH reduces food intake.The majority of studies on the MC system have focused on the hypothalamus.Anatomical evidence,however,clearly indicates that potentially relevant components of the MC system are present in the hindbrain.The caudal brainstem plays a pivotal role in controlling meal size,because it receives direct neural and humoral feedback signals from the gut.Satiation signals such as gastric distention or nutrients in the intestine reach the nucleus tractus solitarius(NTS) via vagal afferent fibers or circulating hormones.NTS neurons respond,principally,with activation of glutamatergic vagal inputs,resulting in the reduction of meal size.It is well established that the regulation of glucose is so important that the brain has glucose-sensing neurons located in key areas such as the hypothalamus,NTS,and amygdala which monitor glucose status in the body and initiate glucoprivic feeding, appropriate sympathoadrenal and neurohumoral responses to maintain homeostasis.Other works have shown that hindbrain catecholaminergic neurons are glucose responsive. glucose-excited neurons(glucose-EXC) increase and glucose-inhibited neurons (glucose-INH) decrease their firing rate when extracellular glucose concentration rises.Object:To investigate the effects ofα-MSH on glucose sensing neurons and gastric distension sensitive neurons in DVC and the possible mechanism by whichα-MSH controls feeding and energy homeostasis.Methods:Electrophysiological method and micro-pressure injection.Recording the firing frequencies of gastric distension neurons and glucose-sensing neurons before and after local administration of 500nMα-MSH in DVC.0.9%NaCl for the control.Results:(1) The 107 neurons were tested with glucose,of which 30 were activated by glucose and identified as glucose-excited(glucose-EXC) neurons;26 were depressed and identified as glucose-inhibited(glucose-INH) neurons;other 51 failed to respond to glucose.Of 24 glucose-excited neurons examined for response toα-MSH,19 were activated,5 failed to respond toα-MSH.Of 20 glucose-inhibited neurons examined for response toα-MSH,16 were depressed,1 was activated,and 3 failed to respond toα-MSH.(2) In addition,there were 62 DVC neurons examined with gastric distension (GD),23 were excited(GD-EXC),19 were inhibited(GD-INH),and 20 failed to respond to GD.15 out of the 20 GD-EXC neurons were excited,whereas 11 out of 14 GD-INH neurons were suppressed byα-MSH.The effects ofα-MSH could be abolished by pretreating with the MC3/4R antagonist,SHU9119(1μM).(3) Four types neurons were failed to respond to 0.9%NaCl.Conclusion:In conclusion,in the present studyα-MSH has been shown to modulate the activity of glucose sensing neurons and GD-sensitive neurons in DVC.The primary effects ofα-MSH are:glucose-EXC neurons are activated byα-MSH and glucose-INH neurons are suppressed byα-MSH;GD-EXC neurons are activated byα-MSH and GD-INH neurons are suppressed byα-MSH.They might be the paths forα-MSH to inhibit food intake.