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Urocortin 3 elevates cytosolic calcium in nucleus ambiguus neurons
Author(s) -
Brailoiu G. Cristina,
Deliu Elena,
Tica Andrei A.,
Chitravanshi Vineet C.,
Brailoiu Eugen
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07869.x
Subject(s) - urocortin , nucleus ambiguus , endocrinology , medicine , ryanodine receptor , receptor , biology , chemistry , medulla oblongata , central nervous system
J. Neurochem . (2012) 122 , 1129–1136. 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.