Glucose increases synaptic transmission from vagal afferent central nerve terminals via modulation of 5-HT3 receptors.
Acute hyperglycemia has profound effects on vagally mediated gastrointestinal functions. We have reported recently that the release of glutamate from the central terminals of vagal afferent neurons is correlated directly with the extracellular glucose concentration. The present study was designed to test the hypothesis that 5-HT(3) receptors present on vagal afferent nerve terminals are involved in this glucose-dependent modulation of glutamatergic synaptic transmission. Whole-cell patch-clamp recordings were made from neurons of the nucleus tractus solitarius (NTS) in thin rat brainstem slices. Spontaneous and evoked glutamate release was decreased in a concentration-dependent manner by the 5-HT(3) receptor selective antagonist, ondansetron. Alterations in the extracellular glucose concentration induced parallel shifts in the ondansetron-mediated inhibition of glutamate release. The changes in excitatory synaptic transmission induced by extracellular glucose concentration were mimicked by the serotonin uptake inhibitor, fenfluramine. These data suggest that glucose alters excitatory synaptic transmission within the rat brainstem via actions on tonically active 5-HT(3) receptors, and the number of 5-HT(3) receptors on vagal afferent nerve terminals is positively correlated with the extracellular glucose concentration. These data indicate that the 5-HT(3) receptors present on synaptic connections between vagal afferent nerve terminals and NTS neurons are a strong candidate for consideration as one of the sites where glucose acts to modulate vagovagal reflexes.
Wan
Shuxia
S
Dept. of Neuroscience, Pennington Biomedical Research Ctr., Louisiana State Univ., Baton Rouge, LA 70808, USA.
Browning
Kirsteen N
KN
D000818:Animals; D001933:Brain Stem / Q000166:cytology; D004594:Electrophysiology; D005071:Evoked Potentials / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism*
D011985:Receptors, Serotonin; D012701:Serotonin; D018698:Glutamic Acid; D005947:Glucose
Naunyn Schmiedebergs Arch Pharmacol. 1997 Jul;356(1):145-50
9228202
J Neurophysiol. 2005 May;93(5):2530-40
15615836
Regul Pept. 2004 Jan 15;117(1):11-23
14687696
Am J Physiol Gastrointest Liver Physiol. 2003 Mar;284(3):G367-72
12409280
J Physiol. 2001 Oct 1;536(Pt 1):141-52
11579164
Am J Physiol Regul Integr Comp Physiol. 2003 May;284(5):R1340-53
12531785
Diabetes Care. 2001 Feb;24(2):371-81
11213895
Brain Res. 1993 May 28;612(1-2):289-98
8330206
Am J Physiol. 1996 Jul;271(1 Pt 2):H80-7
8760161
Physiol Behav. 1997 Jan;61(1):93-100
8976538
Annu Rev Physiol. 2006;68:279-305
16460274
Neuroscience. 2000;95(3):881-92
10670455
Exp Physiol. 2005 Mar;90(2):175-81
15604109
Am J Physiol Gastrointest Liver Physiol. 2001 Jun;280(6):G1055-60
11352796
Diabetes. 1997 Sep;46 Suppl 2:S77-81
9285504
Brain Res. 1998 Apr 27;791(1-2):229-34
9593908
Brain Res. 2005 Aug 9;1052(2):139-46
16005442
J Neurosci. 2002 Sep 15;22(18):8222-9
12223576
J Physiol. 2005 Aug 1;566(Pt 3):939-53
15905216
Am J Physiol. 1990 Oct;259(4 Pt 2):H1307-11
1977326
Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G798-808
11518692
Neuroscience. 1981;6(4):557-618
7017455
J Physiol. 2001 Nov 1;536(Pt 3):753-67
11691870
Brain Res Bull. 2001 Nov 15;56(5):425-39
11750788
J Comp Neurol. 1989 May 8;283(2):248-68
2738198
J Auton Nerv Syst. 1986 Jul;16(3):159-70
3745773
Obes Res. 1995 Dec;3 Suppl 5:735S-740S
8653556
Gastroenterology. 1976 Feb;70(2):190-6
765178
Am J Physiol. 1988 Aug;255(2 Pt 2):R200-4
3044143
Am J Physiol. 1990 Dec;259(6 Pt 2):R1131-8
2260724
Brain Res. 1992 Aug 28;589(1):62-8
1422823
J Physiol. 1996 Feb 15;491 ( Pt 1):177-85
9011609
Adv Exp Med Biol. 1981;133:7-35
7032251
Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G757-63
18202107
J Physiol. 2001 Feb 1;530(Pt 3):431-42
11158274
Gut. 2002 Jul;51 Suppl 1:i11-4
12077056
Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G916-23
11557511
Neuroscience. 1990;38(3):667-73
2176720
Am J Physiol Regul Integr Comp Physiol. 2004 Oct;287(4):R817-23
15191908
Am J Physiol Regul Integr Comp Physiol. 2007 Mar;292(3):R1092-100
17122331
J Auton Nerv Syst. 1997 Apr 14;63(3):127-36
9138244
Diabet Med. 1996 Sep;13(9 Suppl 5):S28-30
8894467
J Neurosci. 2005 Apr 6;25(14):3578-85
15814788
Neuroreport. 1999 Aug 20;10(12):2657-60
10574387
Annu Rev Physiol. 2002;64:355-405
11826273
Physiol Rev. 2001 Apr;81(2):929-69
11274347
Neurosci Lett. 2000 Jan 7;278(1-2):77-80
10643805
Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G692-8
17656445
J Physiol. 2006 Sep 15;575(Pt 3):761-76
16825311
Curr Treat Options Gastroenterol. 2001 Apr;4(2):179-191
11469976
Diabetes Care. 2003 May;26(5):1553-79
12716821
J Auton Nerv Syst. 1995 Mar 2;51(3):191-7
7769152
Am J Physiol Gastrointest Liver Physiol. 2008 May;294(5):G1158-64
18356537
J Neurosci. 2007 Aug 22;27(34):8979-88
17715335
J Neurosci. 1994 Aug;14(8):5068-76
8046468
Aliment Pharmacol Ther. 2003 Nov 15;18(10):1039-48
14616171
Am J Physiol Regul Integr Comp Physiol. 2003 Nov;285(5):R1192-202
12869364
Diabet Med. 1996 Sep;13(9 Suppl 5):S16-22
8894465
News Physiol Sci. 1998 Dec;13:275-280
11390803
J Neurophysiol. 2005 Oct;94(4):2763-71
16093341
Neurosci Lett. 1995 May 19;191(1-2):75-8
7659296
Neuroscience. 1994 Mar;59(1):195-210
7514769
J Physiol. 1996 Feb 15;491 ( Pt 1):163-76
9011608
Am J Physiol. 1997 Mar;272(3 Pt 2):H1250-9
9087599
J Physiol. 1998 Jun 15;509 ( Pt 3):717-27
9596794
Neuropharmacology. 1997 Apr-May;36(4-5):489-98
9225274
Brain Res. 1994 Mar 28;641(1):163-6
8019844
J Physiol. 2001 Feb 1;530(Pt 3):343
11158267
Eur J Pharmacol. 1993 Oct 12;243(1):13-8
8253120
J Comp Neurol. 2003 Sep 29;464(4):525-39
12900922
Neurosci Lett. 1990 Jun 22;114(1):22-6
1696365
J Physiol. 1978 Sep;282:485-506
722554
J Physiol. 2006 Feb 1;570(Pt 3):469-84
16284073
Brain Res. 1984 Jul 30;307(1-2):109-16
6147174
Neuropharmacology. 1989 Dec;28(12):1367-76
2559349
J Comp Neurol. 1987 Nov 8;265(2):275-93
2447131
J Physiol. 2007 Mar 15;579(Pt 3):691-702
17218356
J Physiol. 1968 Mar;195(2):481-92
4296699
Brain Res. 2004 Dec 3;1028(2):156-69
15527741