Leptin excites enteric neurons of guinea-pig submucous and myenteric plexus

Background Leptin, one of the most prominent mediators released from adipocytes, influences neuronal activity in the central nervous system. The enteric nervous system (ENS) expresses leptin receptors but consequence of activation of these receptors on enteric neuron activity has not been systematically studied. An adipocyte-ENS axis is suggested by close apposition between enteric nerves and adipocytes. The aim of this study was to investigate the effects of leptin on guinea-pig submucous and myenteric neurons. Methods Using voltage sensitive dye imaging, we recorded neural responses to application of leptin (0.0625 nmol L-1) in myenteric and submucous neurons, nicotine (10 mu mol L-1) served as a reference for neuronal excitation. Mucosal ion secretion and muscle activity were measured in vitro with Ussing and organ bath techniques, respectively. Key Results Leptin induced spike discharge in 13.6% of submucous neurons and in 8.2% of myenteric neurons (1.1 +/- 0.9 and 1.2 +/- 1.0 Hz, respectively). Although there was an overlap of nicotine and leptin responses, 38.5% of submucous and 25% of myenteric neurons activated by leptin did not respond to nicotine. Leptin did not inhibit ongoing spike discharge or fast excitatory postsynaptic potentials. Leptin (0.0625 nmol L-1) did not affect mucosal secretion or muscle activity suggesting a subtle modulatory action of leptin at the level of the ENS. Conclusions & Inferences Leptin activates submucous and myenteric neurons indicating relevance for adipocyte-ENS signaling. These results set the basis for further studies to reveal the functional correlate of the neural action of leptin in the ENS.