title: Effects of VPAC1 activation in nucleus ambiguus neurons.
abstract: 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 Ca2+mobilization, membrane depolarization and activation of P/Q-type Ca2+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.
authors.affiliation: Department of Pharmacology, University of Medicine and Pharmacy, Craiova, Romania.
authors.forename: Florin Liviu
authors.initials: FL
authors.lastname: Gherghina
authors.affiliation: Department of Pharmacology, University of Medicine and Pharmacy, Craiova, Romania.
authors.forename: Andrei Adrian
authors.initials: AA
authors.lastname: Tica
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Deliu
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Abood
authors.affiliation: Department of Pharmaceutical Sciences, Thomas Jefferson University, Jefferson College of Pharmacy, Philadelphia, PA 19107, USA.
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
authors.affiliation: Center for Substance Abuse Research, Temple University School of Medicine, Philadelphia, PA 19140, USA. Electronic address: ebrailou@temple.edu.
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000139:chemically induced / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000819:agonists / Q000378:metabolism*; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D010276:Parasympatholytics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D002118:Calcium
keywords: Autonomic cardiac tone; Bradycardia; Calcium signaling; PACAP