title: Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons.
abstract: Urocortin 3 (also known as stresscopin) is an endogenous ligand for the corticotropin-releasing factor receptor 2 (CRF(2)). Despite predominant G(s) coupling of CRF(2), promiscuous coupling with other G proteins has been also associated with the activation of this receptor. As urocortin 3 has been involved in central cardiovascular regulation at hypothalamic and medullary sites, we examined its cellular effects on cardiac vagal neurons of nucleus ambiguus, a key area for the autonomic control of heart rate. Urocortin 3 (1 nM-1000 nM) induced a concentration-dependent increase in cytosolic Ca(2+) concentration that was blocked by the CRF(2) antagonist K41498. In the case of two consecutive treatments with urocortin 3, the second urocortin 3-induced Ca(2+) response was reduced, indicating receptor desensitization. The effect of urocortin 3 was abolished by pre-treatment with pertussis toxin and by inhibition of phospolipase C with U-73122. Urocortin 3 activated Ca(2+) influx via voltage-gated P/Q-type channels as well as Ca(2+) release from endoplasmic reticulum. Urocortin 3 promoted Ca(2+) release via inositol 1,4,5 trisphosphate receptors, but not ryanodine receptors. Our results indicate a novel Ca(2+) -mobilizing effect of urocortin 3 in vagal pre-ganglionic neurons of nucleus ambiguus, providing a cellular mechanism for a previously reported role for this peptide in parasympathetic cardiac regulation.
authors: Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140, USA. ebrailou@temple.edu
authors: G Cristina
authors: GC
authors: Brailoiu
authors: Elena
authors: E
authors: Deliu
authors: Andrei A
authors: AA
authors: Tica
authors: Vineet C
authors: VC
authors: Chitravanshi
authors: Eugen
authors: E
authors: Brailoiu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism*; D005260:Female; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology; D054832:Urocortins / Q000502:physiology*; D014630:Vagus Nerve / Q000166:cytology* / Q000378:metabolism / Q000502:physiology
chemical_list: D054832:Urocortins; C514216:urocortin 3, rat; D003346:Corticotropin-Releasing Hormone; D002118:Calcium