Insulin-like growth factor-1 inhibits adult supraoptic neurons via complementary modulation of mechanoreceptors and glycine receptors.
In the CNS, insulin-like growth factor-1 (IGF-1) is mainly known for its trophic effect both during development and in adulthood. Here, we show than in adult rat supraoptic nucleus (SON), IGF-1 receptor immunoreactivity is present in neurons, whereas IGF-1 immunoreactivity is found principally in astrocytes and more moderately in neurons. In vivo application of IGF-1 within the SON acutely inhibits the activity of both vasopressin and oxytocin neurons, the two populations of SON neuroendocrine cells. Recordings of acutely isolated SON neurons showed that this inhibition occurs through two rapid and reversible mechanisms, both involving the neuronal IGF-1 receptor but different intracellular messengers. IGF-1 inhibits Gd3+-sensitive and osmosensitive mechanoreceptor cation current via phosphatidylinositol-3 (PI3) kinase activation. IGF-1 also potentiates taurine-activated glycine receptor (GlyR) Cl- currents by increasing the agonist sensitivity through a extremely rapid (within a second) PI3 kinase-independent mechanism. Both mechanoreceptor channels and GlyR, which form the excitatory and inhibitory components of SON neuron osmosensitivity, are active at rest, and their respective inhibition and potentiation will both be inhibitory, leading to strong decrease in neuronal activity. It will be of interest to determine whether IGF-1 is released by neurons, thus participating in an inhibitory autocontrol, or astrocytes, then joining the growing family of glia-to-neuron transmitters that modulate neuronal and synaptic activity. Through the opposite and complementary acute regulation of mechanoreceptors and GlyR, IGF-1 appears as a new important neuromodulator in the adult CNS, participating in the complex integration of neural messages that regulates the level of neuronal excitability.
Ster
Jeanne
J
Biologie des Neurones Endocrines, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 5101, Institut National de la Santé et de la Recherche Médicale de Pharmacologie et d'Endocrinologie, 34094 Montpellier Cedex 5, France.
Colomer
Claude
C
Monzo
Cécile
C
Duvoid-Guillou
Anne
A
Moos
Françoise
F
Alonso
Gérard
G
Hussy
Nicolas
N
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018684:Glycine Agents / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D018009:Receptors, Glycine / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000166:cytology*; D013654:Taurine / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D018684:Glycine Agents; D018009:Receptors, Glycine; D014316:Tritium; D014667:Vasopressins; D013654:Taurine; D010121:Oxytocin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D013331:Strychnine; D000077191:Wortmannin
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