Central Effects Of Motilin Receptor Agonist-erythromycin On The Glucoresponsive Neurons In Hypothalamus

Background Motilin is a 22-amino-acid peptide that released periodically during fasting and it regulates the interdigestive migrating complex of the upper gastrointestinal tract. Recent researches demonstrate that motilin immunoreactivity, motilin mRNA and its receptors were found in several regions of the brain, such as hippocampus, amygdala, hypothalamus and cerebellum. Moreover, It has been confirmed that i. c. v. administration of motilin increased food intake in mice.Considerable evidences support the view that the lateral hypothalamic area (LHA) and the ventromedial hypothalamic nucleus (VMH) have historically been implicated in ingestive behavior, energy balance and body mass regulation. The LHA is more closely associated with the initiation of eating) whereas the VMH mediates the cessation of eating. Glucoresponsive neurons in LHA and VMH are important in feeding control.Aims The purpose of this study was to examine the effects of erythromycin, a motilin receptor agonist, on neural activity of GSNs and GRNs in LHA and VMH.Method (1) Extracellular recordings were made from single neuron in region of LHA and VMH in ansthetized rats. On the basis of their responsiveness to intracarotid injection of glucose, neurons in LHA which decreased in activities were characterized as GSNs and the neurons in VMH which increased in activities were identified as GRNs. (2)Effects of the i. c. v. administration of 4g/ L EM 1 L or mixture of EM and GM-109 1 L on neuronal activity of the glucoresponsive neurons and non-glucoresponsive neurons in hypothalamus were examined.Results (1)In 24 LHA neurons of 51, intracarotid injection of glucose solution suppressed the neuronal activity .compared wilh that of 0. 28M NaCl solution; 14VMH neurons(58%) of 24 .increased their firing rate during or after injection of glucose solution, and these neurons had no response to 0. 28M NaCl solution. They were identifiedas GSNs and GRNs respectively. (2)In LHA, 18(66. 7%) GSNs were excited by i. c. v. administration of EM. Their average firing rates increased by 56. 49 ?12. 12% (P< 0.01). We also observed 6 (27. 9%) Non-GSNs were excited by EM. In VMH, EM suppressed the activities of 9(25%) GRNs and their firing rate decreased by 27. 91 ?7. 42%(P<0. 01) , only 2 Non-GRNs had the same response. (3)i. c. v. administration of mixture of EM and GM-109 IpL, produced no effect in GSNs and GRNs which were sensitive to i. c. v. administration of EM.Conclusion These results indicate that EM, a MT receptor agonist, can modulate the activities of LHA-GSNs and VMH-GRNs and this may contribute to motilin's effect on feeding behavior.