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The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces inositol 1,4,5-trisphosphate receptor-mediated Ca 2+ mobilization, membrane depolarization and activation of P/Q-type Ca 2+ channels. In vivo, this pathway converges onto transient reduction in heart rate of conscious rats. Therefore we demonstrate a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart rate, adding to the complexity of PACAP-mediated cardiovascular modulation.

Competing Interests: statement All authors declare that there are no conflicts of interest.

Titel:	Effects of VPAC1 activation in nucleus ambiguus neurons.
Autor/in / Beteiligte Person:	Gherghina, FL ; Tica, AA ; Deliu, E ; Abood, ME ; Brailoiu, GC ; Brailoiu, E
Link:	Zum Volltext
Zeitschrift:	Brain research, Jg. 1657 (2017-02-15), S. 297
Veröffentlichung:	Amsterdam Elsevier/North-Holland Biomedical Press., 2017
Medientyp:	academicJournal
ISSN:	1872-6240 (electronic)
DOI:	10.1016/j.brainres.2016.12.026
Schlagwort:	Animals Blood Pressure drug effects Blood Pressure physiology Bradycardia chemically induced Bradycardia metabolism Calcium metabolism Calcium Signaling drug effects Calcium Signaling physiology Cells, Cultured Endoplasmic Reticulum drug effects Endoplasmic Reticulum metabolism Female Heart Rate drug effects Heart Rate physiology Male Medulla Oblongata cytology Medulla Oblongata drug effects Membrane Potentials drug effects Membrane Potentials physiology Neuroanatomical Tract-Tracing Techniques Neurons cytology Neurons drug effects Parasympatholytics pharmacology Rats, Sprague-Dawley Receptors, Vasoactive Intestinal Polypeptide, Type I agonists Vagus Nerve cytology Vagus Nerve drug effects Vagus Nerve metabolism Medulla Oblongata metabolism Neurons metabolism Receptors, Vasoactive Intestinal Polypeptide, Type I metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Brain Res] 2017 Feb 15; Vol. 1657, pp. 297-303. <i>Date of Electronic Publication: </i>2016 Dec 30. MeSH Terms: Medulla Oblongata / metabolism ; Neurons / metabolism ; Receptors, Vasoactive Intestinal Polypeptide, Type I / *metabolism ; Animals ; Blood Pressure / drug effects ; Blood Pressure / physiology ; Bradycardia / chemically induced ; Bradycardia / metabolism ; Calcium / metabolism ; Calcium Signaling / drug effects ; Calcium Signaling / physiology ; Cells, Cultured ; Endoplasmic Reticulum / drug effects ; Endoplasmic Reticulum / metabolism ; Female ; Heart Rate / drug effects ; Heart Rate / physiology ; Male ; Medulla Oblongata / cytology ; Medulla Oblongata / drug effects ; Membrane Potentials / drug effects ; Membrane Potentials / physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons / cytology ; Neurons / drug effects ; Parasympatholytics / pharmacology ; Rats, Sprague-Dawley ; Receptors, Vasoactive Intestinal Polypeptide, Type I / agonists ; Vagus Nerve / cytology ; Vagus Nerve / drug effects ; Vagus Nerve / metabolism References: Am J Physiol. 1992 Dec;263(6 Pt 2):H1659-69. (PMID: 1481892) ; Neuroendocrinology. 1993 Jun;57(6):1092-6. (PMID: 7901784) ; Curr Hypertens Rep. 2016 Mar;18(3):22. (PMID: 26849575) ; Am J Physiol. 1995 Jul;269(1 Pt 2):H135-9. (PMID: 7631841) ; Regul Pept. 1996 Apr 23;62(2-3):125-30. (PMID: 8795075) ; J Mol Neurosci. 2002 Feb-Apr;18(1-2):29-35. (PMID: 11931347) ; Regul Pept. 2002 Jan 15;103(1):59-65. (PMID: 11738249) ; Neurosci Lett. 1994 Aug 1;176(2):193-6. (PMID: 7830945) ; J Neurochem. 2013 Sep;126(6):739-48. (PMID: 23795642) ; Neuroscience. 2003;116(2):573-82. (PMID: 12559112) ; J Comp Neurol. 2004 Aug 30;476(4):388-413. (PMID: 15282712) ; J Neurophysiol. 2003 Sep;90(3):1581-8. (PMID: 12761284) ; Am J Physiol Regul Integr Comp Physiol. 2014 Jun 1;306(11):R814-22. (PMID: 24694382) ; Am J Physiol Heart Circ Physiol. 2012 Oct 1;303(7):H910-7. (PMID: 22886412) ; Am J Physiol Regul Integr Comp Physiol. 2001 Aug;281(2):R495-501. (PMID: 11448853) ; Bull Tokyo Dent Coll. 2002 Feb;43(1):31-9. (PMID: 12013823) ; Endocr Rev. 2000 Dec;21(6):619-70. (PMID: 11133067) ; J Neurochem. 2014 May;129(4):628-36. (PMID: 24521102) ; Peptides. 1997;18(10):1555-60. (PMID: 9437716) ; Regul Pept. 2002 Jul 15;107(1-3):115-23. (PMID: 12137973) ; Br J Pharmacol. 2012 May;166(1):42-50. (PMID: 21951273) ; Neuroscience. 2012 May 17;210:58-66. (PMID: 22425752) ; J Pharmacol Exp Ther. 2002 Jan;300(1):78-82. (PMID: 11752100) ; J Biol Chem. 1985 Mar 25;260(6):3440-50. (PMID: 3838314) ; Pharmacol Ther. 2009 Mar;121(3):294-316. (PMID: 19109992) ; J Pharmacol Exp Ther. 2005 Sep;314(3):1322-7. (PMID: 15947034) ; Physiol Rep. 2015 Jun;3(6):null. (PMID: 26038469) ; J Physiol. 2013 Sep 1;591(17):4223-35. (PMID: 23878371) ; Naunyn Schmiedebergs Arch Pharmacol. 1996 Oct;354(4):424-30. (PMID: 8897444) ; Regul Pept. 1995 Dec 14;60(2-3):193-200. (PMID: 8746546) ; Biochemistry. 2000 Aug 15;39(32):9771-7. (PMID: 10933794) ; Pharmacol Rev. 2009 Sep;61(3):283-357. (PMID: 19805477) ; Neuroscience. 2004;129(1):235-41. (PMID: 15489045) ; Brain Res. 1997 Feb 14;748(1-2):189-94. (PMID: 9067461) ; J Neurochem. 2012 Sep;122(6):1129-36. (PMID: 22774996) ; Respir Physiol Neurobiol. 2010 Nov 30;174(1-2):65-75. (PMID: 20470908) Grant Information: P30 DA013429 United States DA NIDA NIH HHS; R01 DA023204 United States DA NIDA NIH HHS; R01 DA035926 United States DA NIDA NIH HHS Contributed Indexing: Keywords: Autonomic cardiac tone; Bradycardia; Calcium signaling; PACAP Substance Nomenclature: 0 (Parasympatholytics) ; 0 (Receptors, Vasoactive Intestinal Polypeptide, Type I) ; SY7Q814VUP (Calcium) Entry Date(s): Date Created: 20170104 Date Completed: 20170807 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC5303116

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Effects of VPAC1 activation in nucleus ambiguus neurons.