α-MSH Influences The Excitability Of Glucosensing Neurons In Rat Hypothalamus

The central melanocortin system plays a significant role in the homeostatic mechanisms which control food intake and energy balance. a-MSH is a biologically active released by polypeptide precursor POMC which undergoes extensive post-translational modification. Some hypothalamic areas is firmly related to the food intake includes the lateral hypothalamic area(LHA),ventrolmedial hypothalamic nucleus,paraventricular nucleus and so on. Among the five melanocortin receptors (MC1-MC5), only MC3R and MC4R are expressed in the hypothalamic areas. The rats were immuned by a-MSH peptide compared with the normal rats had an apparent rise on the food intake, meanwhile administration of a-MSH in the fourth ventricular and the dorsomedial vagal (DMV) would reduce the food intake. We have known that in the LHA has a large proportion of glucose-inhibited neurons, and a large proportion of glucose-excited neurons in the VMH, while both of them in the PVN. Peripheral or central administration of glucose on LHA GI neurons causes an inhibitory effect on food intake had an suppressed interaction with VMH GE neurons which appeared to an excitatory effect. We guess that the glucosensing neurons in hypothalamus is one of the active targets of a-MSH.ObjectiveTo examine the effects of a-MSH on glucosensing neurons in rat lateral hypothalamic area (LHA),ventromedial hypothalamic nucleus (VMH),paraventricular nucleus(PVN).MethodsElectrophysiological recording was adopted to investigate the changes in firing rate of glucosensing neurons after microinjection of a-MSH or pre-administration of SHU9119 into hypothalamus.Results(1) The extracellular activity of 78 neurons was recorded in the LHA,46.15%(36/78) were identified as glucose-inhibited (GI) neurons. Of 36 GI neurons examined for response to a-MSH,75%(27/36) were depressed by a-MSH. a-MSH induced inhibitory response in 19 GI neurons was abolished partly by pre-administration of the MC4-R antagonist SHU9119.(2) The extracellular activity of 56 neurons was recorded in the VMH,39.28%(22/56) were identified as glucose-excited (GE) neurons. Of 22 GE neurons examined for response to aMSH,90.9%(20/22) were activated by aMSH.α-MSH-induced excitatory response in 10 GE neurons was abolished by pre-administration of SHU9119.(3) The extracellular activity of 68 neurons was recorded in the PVN,29.41%(20/68) were identified as glucose-inhibited (GI) neurons, and 39.71%(27/68) were identified as glucose-excited (GE) neurons. Of 27 GE neurons examined for response to aMSH,88.88% (24/27) were activated by a-MSH. Of 20 GI neurons examined for response to aMSH,70% (14/20) were depressed by a-MSH. Both of a-MSH-induced inhibitory response in 7 GI neurons and a-MSH-induced excitatory response in 18 GE neurons was abolished partly by pre-administration of SHU9119.ConclusionThe predominant effect of a-MSH on the electrical activity in the LHA GI neurons is inhibitory, the main effect of a-MSH on the electrical activity in the VMH GE neurons is excitatory, and the GE and GI neurons in the PVN can be modulated by a-MSH. These findings indicate that a-MSH regulates the food intake and energy balance may partly through the action in hypothalamic glucosensing neurons.