Glucagon-like peptide-1 evokes action potentials and increases cytosolic Ca2+ in rat nodose ganglion neurons.
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.
Kakei
Masafumi
M
Department of Geriatric Medicine, Akita University School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. kakei@med.akita-u.ac.jp
Yada
Toshihiko
T
Nakagawa
Atsushi
A
Nakabayashi
Hajime
H
D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000494:pharmacology* / Q000502:physiology; D052216:Glucagon-Like Peptide 1; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009620:Nodose Ganglion / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000494:pharmacology* / Q000502:physiology; D011498:Protein Precursors / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D002118:Calcium