title: Hydrogen sulfide selectively potentiates central preganglionic fast nicotinic synaptic input in mouse superior mesenteric ganglion.
abstract: Hydrogen sulfide (H2S) plays important roles in the enteric system in the wall of the gastrointestinal tract. There have been no studies on whether H2S is endogenously generated in peripheral sympathetic ganglia and, if so, its effect on synaptic transmission. In this study, we examined the effect of H2S on cholinergic excitatory fast synaptic transmission in the mouse superior mesenteric ganglion (SMG). Our study revealed that NaHS and endogenously generated H2S selectively potentiated cholinergic fast EPSPs (F-EPSPs) evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. The H2S-producing enzyme cystathionine-γ-lyase (CSE) was expressed in both neurons and glial cells. The CSE blocker PAG (dl-propargylglycine) significantly reduced the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Inhibiting the breakdown of endogenously generated H2S with stigmatellin potentiated the amplitude of F-EPSPs evoked by splanchnic nerve stimulation but not F-EPSPs evoked by colonic nerve stimulation. Splanchnic F-EPSPs but not colonic F-EPSPs were reduced in CSE knock-out (KO) mice. Functional studies showed that NaHS enhanced the inhibitory effect of splanchnic nerve stimulation on colonic motility. Colonic motility in CSE-KO mice was significantly higher than colonic motility in wild-type mice. We conclude that endogenously generated H2S acted selectively on presynaptic terminals of splanchnic nerves to modulate fast cholinergic synaptic input and that this effect of H2S modulates CNS control of gastrointestinal motility. Our results show for the first time that the facilitatory effect of endogenous H2S in the mouse SMG is pathway specific.
authors.affiliation: Enteric NeuroScience Program, Department of Physiology and Biomedical Engineering, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Sha
authors.forename: David R
authors.initials: DR
authors.lastname: Linden
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Szurszewski
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000502:physiology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D044683:Colon, Descending / Q000294:innervation; D003542:Cystathionine gamma-Lyase / Q000172:deficiency; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000235:genetics; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics; D006168:Guinea Pigs; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013153:Splanchnic Nerves / Q000502:physiology; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D058787:GABA-A Receptor Antagonists; C493461:Slc18a3 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D003542:Cystathionine gamma-Lyase; D000109:Acetylcholine; D006862:Hydrogen Sulfide
references.citation: Biochem Biophys Res Commun. 2000 Jan 7;267(1):129-33
references.pmid: 10623586
references.citation: J Physiol. 1993 Nov;471:175-89
references.pmid: 7907143
references.citation: J Physiol. 2004 Oct 1;560(Pt 1):231-47
references.pmid: 15284351
references.citation: Neurochem Int. 2010 Jan;56(1):3-10
references.pmid: 19703504
references.citation: Pain. 2007 Nov;132(1-2):74-81
references.pmid: 17346888
references.citation: J Physiol. 1993 Nov;471:191-207
references.pmid: 8120803
references.citation: Antioxid Redox Signal. 2008 Jan;10(1):31-42
references.pmid: 17956188
references.citation: Science. 2008 Oct 24;322(5901):587-90
references.pmid: 18948540
references.citation: Neuron. 2007 Feb 15;53(4):563-75
references.pmid: 17296557
references.citation: Pain. 2009 Mar;142(1-2):127-32
references.pmid: 19167819
references.citation: Br J Pharmacol. 2012 Apr;165(7):2178-90
references.pmid: 21950400
references.citation: Am J Physiol. 1997 Feb;272(2 Pt 1):G357-66
references.pmid: 9124361
references.citation: Gut. 2009 Jun;58(6):751-61
references.pmid: 18852258
references.citation: J Clin Invest. 1999 Oct;104(8):1107-14
references.pmid: 10525049
references.citation: Neurochem Int. 2010 Feb;56(3):508-15
references.pmid: 20026367
references.citation: Antioxid Redox Signal. 2012 Jul 1;17(1):1-10
references.pmid: 22369066
references.citation: Neuron. 1995 Apr;14(4):795-802
references.pmid: 7718241
references.citation: J Neurosci. 1996 Feb 1;16(3):1066-71
references.pmid: 8558235
references.citation: Neuron. 1999 Aug;23(4):821-32
references.pmid: 10482247
references.citation: J Physiol. 1979 Apr;289:449-68
references.pmid: 458680
references.citation: Chin J Physiol. 1999 Dec 31;42(4):201-10
references.pmid: 10707895
references.citation: Gastroenterology. 2006 Nov;131(5):1542-52
references.pmid: 17101327
references.citation: Glia. 2006 Aug 1;54(2):116-24
references.pmid: 16718684
references.citation: J Neurophysiol. 2011 Oct;106(4):1822-32
references.pmid: 21734104
references.citation: J Neurochem. 2008 Aug;106(4):1577-85
references.pmid: 18513201
references.citation: Physiol Rev. 2012 Apr;92(2):791-896
references.pmid: 22535897
references.citation: Neuropharmacology. 1982 May;21(5):397-403
references.pmid: 7110528
references.citation: Antioxid Redox Signal. 2010 May 1;12(9):1135-46
references.pmid: 19769466
references.citation: J Comp Neurol. 2003 Apr 21;459(1):25-43
references.pmid: 12629665
references.citation: FASEB J. 2010 Oct;24(10):3840-9
references.pmid: 20543114
references.citation: Br J Pharmacol. 2004 May;142(1):31-4
references.pmid: 15051627
references.citation: Eur J Neurosci. 2007 Mar;25(5):1307-18
references.pmid: 17425557
references.citation: J Neurophysiol. 1993 Jul;70(1):81-96
references.pmid: 8395590
references.citation: Dig Dis Sci. 1991 Jul;36(7):998-1018
references.pmid: 2070711
references.citation: Neurogastroenterol Motil. 2002 Aug;14(4):339-48
references.pmid: 12213101
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1983 Apr;322(3):210-5
references.pmid: 6306485
references.citation: FASEB J. 2004 Mar;18(3):557-9
references.pmid: 14734631
references.citation: Biochim Biophys Acta. 2010 Aug;1797(8):1500-11
references.pmid: 20398623
references.citation: Neurogastroenterol Motil. 2010 Nov;22(11):1224-31, e319-20
references.pmid: 20659296
references.citation: J Biol Chem. 2010 Jul 16;285(29):21903-7
references.pmid: 20448039
references.citation: Biochem Biophys Res Commun. 1997 Aug 28;237(3):527-31
references.pmid: 9299397