Glucagon-like peptide-1 Evokes Action Potentials and Increases Cytosolic Ca2+ in Rat Nodose Ganglion Neurons

Auton Neurosci. 2002 Nov 29;102(1-2):39-44. doi: 10.1016/s1566-0702(02)00182-0.


We previously reported that the intraportal appearance of glucagon-like peptide-1 (GLP-1) facilitates the afferent activity (the spike discharge firing rate) of the rat hepatic vagus in a dose-dependent fashion. To examine whether GLP-1 directly activates single neurons isolated from the rat nodose ganglion, GLP-1-induced changes of the membrane potential and cytosolic-free Ca2+ concentration ([Ca2+]i) in the cells were measured using whole-cell patch-clamp and microfluorometric techniques, respectively. GLP-1 application (3 x 10(-12) - 3 x 10(-9) M) induced a gradual depolarization from a mean resting membrane potential of - 55.0 +/- 3.1 mV and evoked a burst of action potentials with a time lag of 7.5 +/- 4.5 min after its starting (n = 4). The burst of action potentials continued during the application and even up to 13 min or more after its cessation. GLP-1 at a concentration of 10(-12) - 10(-8) M induced an increase of [Ca2+]i. The GLP-1-induced [Ca2+]i responses were often oscillatory and lasted even up to 10 min or more after the washout of GLP-1. An adenylate cyclase activator, forskolin, mimicked the GLP-1-induced increase in [Ca2+]i. The present results indicate that GLP-1 activates nodose ganglion neurons as manifested by membrane depolarization, a burst of action potentials and [Ca2+]i increase, possibly via the cAMP pathway. Together with our previous observations, the results strongly suggest cellular mechanisms by which the postprandial humoral information, intraportal appearance of GLP-1, is uniquely converted to the neural information in the hepatoportal area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Calcium / metabolism*
  • Cytosol / drug effects*
  • Cytosol / metabolism
  • Dose-Response Relationship, Drug
  • Glucagon / pharmacology*
  • Glucagon / physiology
  • Glucagon-Like Peptide 1
  • Male
  • Membrane Potentials / physiology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Nodose Ganglion / drug effects*
  • Nodose Ganglion / metabolism
  • Patch-Clamp Techniques
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / physiology
  • Protein Precursors / pharmacology*
  • Protein Precursors / physiology
  • Rats
  • Rats, Wistar


  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Calcium