Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons

J Neurochem. 2012 Sep;122(6):1129-36. doi: 10.1111/j.1471-4159.2012.07869.x. Epub 2012 Aug 3.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium / metabolism
  • Calcium / physiology*
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Corticotropin-Releasing Hormone / physiology*
  • Cytosol / metabolism*
  • Female
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / physiology
  • Neurons / metabolism
  • Neurons / physiology*
  • Parasympathetic Nervous System / cytology
  • Parasympathetic Nervous System / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / physiology
  • Urocortins / physiology*
  • Vagus Nerve / cytology*
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiology


  • Urocortins
  • urocortin 3, rat
  • Corticotropin-Releasing Hormone
  • Calcium