title: Insulin-like growth factor-1 inhibits adult supraoptic neurons via complementary modulation of mechanoreceptors and glycine receptors.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Ster
authors.forename: Claude
authors.initials: C
authors.lastname: Colomer
authors.forename: Cécile
authors.initials: C
authors.lastname: Monzo
authors.forename: Anne
authors.initials: A
authors.lastname: Duvoid-Guillou
authors.forename: Françoise
authors.initials: F
authors.lastname: Moos
authors.forename: Gérard
authors.initials: G
authors.lastname: Alonso
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hussy
mesh_terms: 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
chemical_list: 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
references.citation: Prog Brain Res. 1998;119:59-76
references.pmid: 10074781
references.citation: Prog Neurobiol. 1999 Apr;57(6):625-55
references.pmid: 10221785
references.citation: Exp Neurol. 1999 Oct;159(2):419-32
references.pmid: 10506513
references.citation: Nature. 1999 Oct 28;401(6756):918-21
references.pmid: 10553907
references.citation: J Neurosci Res. 2000 Feb 1;59(3):332-41
references.pmid: 10679768
references.citation: J Physiol. 2000 Mar 1;523 Pt 2:291-9
references.pmid: 10699075
references.citation: J Neurosci. 2000 Apr 15;20(8):2926-33
references.pmid: 10751445
references.citation: J Neurophysiol. 2000 Apr;83(4):2332-48
references.pmid: 10758137
references.citation: Neuron. 2000 Mar;25(3):635-47
references.pmid: 10774731
references.citation: Nat Neurosci. 2000 Jun;3(6):572-9
references.pmid: 10816313
references.citation: Prog Neurobiol. 2000 Oct;62(2):113-34
references.pmid: 10828380
references.citation: Nat Neurosci. 2000 Aug;3(8):757-8
references.pmid: 10903566
references.citation: Neuroscience. 2000;99(4):751-60
references.pmid: 10974438
references.citation: J Neurosci Res. 2000 Nov 1;62(3):357-62
references.pmid: 11054804
references.citation: J Neurosci. 2000 Nov 15;20(22):8435-42
references.pmid: 11069951
references.citation: Biochemistry. 2000 Dec 26;39(51):15705-12
references.pmid: 11123895
references.citation: J Neurosci. 2001 Mar 1;21(5):1628-34
references.pmid: 11222653
references.citation: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5880-5
references.pmid: 11320223
references.citation: Neuroreport. 2001 May 8;12(6):1293-6
references.pmid: 11338209
references.citation: J Neurosci. 2001 Sep 15;21(18):7110-6
references.pmid: 11549721
references.citation: J Physiol. 2002 Mar 1;539(Pt 2):495-502
references.pmid: 11882681
references.citation: Nat Neurosci. 2002 Apr;5(4):299-300
references.pmid: 11889470
references.citation: Brain Res Bull. 2002 Mar 15;57(5):721-5
references.pmid: 11927377
references.citation: Trends Neurosci. 2002 Apr;25(4):199-205
references.pmid: 11998688
references.citation: Cancer Res. 2002 May 15;62(10):2942-50
references.pmid: 12019176
references.citation: J Physiol. 2002 Jul 15;542(Pt 2):413-29
references.pmid: 12122142
references.citation: Prog Brain Res. 2002;139:85-94
references.pmid: 12436928
references.citation: Prog Brain Res. 2002;139:95-112
references.pmid: 12436929
references.citation: Physiol Behav. 2002 Dec;77(4-5):565-9
references.pmid: 12527000
references.citation: J Neurophysiol. 2003 Jun;89(6):3008-17
references.pmid: 12612011
references.citation: J Physiol. 1992 Sep;455:291-306
references.pmid: 1362442
references.citation: Neuroendocrinology. 1992 Dec;56(6):856-63
references.pmid: 1369595
references.citation: Mol Cell Neurosci. 2003 Sep;24(1):23-40
references.pmid: 14550766
references.citation: Prog Brain Res. 2004;146:137-50
references.pmid: 14699962
references.citation: Endocrinology. 1994 Nov;135(5):1753-61
references.pmid: 7525251
references.citation: Trends Neurosci. 1994 Aug;17(8):340-4
references.pmid: 7526505
references.citation: Trends Neurosci. 1995 Mar;18(3):143-50
references.pmid: 7754526
references.citation: J Neurosci. 1994 Nov;14(11 Pt 1):6412-22
references.pmid: 7965046
references.citation: Exp Physiol. 1996 Jul;81(4):577-85
references.pmid: 8853267
references.citation: J Physiol. 1996 Oct 15;496 ( Pt 2):491-501
references.pmid: 8910232
references.citation: Neuroreport. 1996 Dec 20;8(1):373-7
references.pmid: 9051813
references.citation: Endocrinology. 1997 Apr;138(4):1427-33
references.pmid: 9075698
references.citation: J Physiol. 1997 Aug 1;502 ( Pt 3):609-21
references.pmid: 9279812
references.citation: Neuron. 1997 Aug;19(2):421-9
references.pmid: 9292730
references.citation: J Neurophysiol. 1997 Nov;78(5):2363-71
references.pmid: 9356388
references.citation: J Physiol. 1998 Mar 1;507 ( Pt 2):463-71
references.pmid: 9518705
references.citation: J Neurobiol. 1998 Jul;36(1):1-15
references.pmid: 9658334
references.citation: J Physiol. 1999 Feb 1;514 ( Pt 3):701-11
references.pmid: 9882741