Glucagon-like peptide 1 receptor mediated modulation of excitatory synaptic transmission in the rat nucleus tractus solitarius

Abstract

Glucagon-like peptide 1 (GLP-1) is an enteroendocrine hormone which is released from L-cells in the intestine and stimulates insulin secretion and inhibits glucagon secretion. It also shows appetite suppressing effects by mainly central action. GLP-1 is also a neuropeptide synthesized by neurons in the nucleus tractus solitarius (NTS). These neurons project to hypothalamic nuclei and release GLP-1 which inhibit food intake. GLP-1 receptors are also expressed in the NTS which is the first gate region receiving sensory vagal inputs from peripheral organs including gastrointestinal organs. However, the physiological roles of the GLP-1 receptors in the NTS were not examined precisely. So, we examined the effects of GLP-1 receptor activation on excitatory synaptic transmission in the NTS second order neurons.

Liraglutide (1 μM: GLP-1 receptor agonist) did not changed the frequency and amplitude of spontaneous EPSCs (sEPSCs) but increased the amplitude of evoked EPSCs (eEPSCs). Paired pulse ratio of eEPSCs was decreased by liraglutide which suggested presynaptic action. Another GLP-1 receptor agonist exendin-4 (1 μM) also showed similar effects with liraglutide on both sEPSCs and eEPSCs.

These results suggest that the activation of GLP-1 receptors in the NTS facilitates evoked excitatory synaptic transmission although no effects on spontaneous synaptic transmission. These effects may partly contribute to the weight reducing effects of GLP-1 agonist.