Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo

Sullivan, Nicole R., Crane, James W., Damjanoska, Katerina J., Carrasco, Gonzalo A., D'Souza,Deborah N., Garcia, Francisca and Van de Kar, Louis D. (2005) Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo. Naunyn-schmiedebergs Archives of Pharmacology, 371 1: 18-26. doi:10.1007/s00210-004-1005-7


Author Sullivan, Nicole R.
Crane, James W.
Damjanoska, Katerina J.
Carrasco, Gonzalo A.
D'Souza,Deborah N.
Garcia, Francisca
Van de Kar, Louis D.
Title Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo
Journal name Naunyn-schmiedebergs Archives of Pharmacology   Check publisher's open access policy
ISSN 0028-1298
1432-1912
Publication date 2005-01
Sub-type Article (original research)
DOI 10.1007/s00210-004-1005-7
Volume 371
Issue 1
Start page 18
End page 26
Total pages 9
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 1115 Pharmacology and Pharmaceutical Sciences
Abstract Tandospirone, an azapirone, is a selective serotonin(1A) (5-HT1A) receptor agonist. The effects of tandospirone on plasma hormones and on mitogen-activated protein (MAP) kinase activity in the brain of male rats were studied. Tandospirone produced a time- and dose-dependent increase in plasma levels of oxytocin, adrenocorticotropin (ACTH), corticosterone, and prolactin. The minimal dose of tandospirone that led to a significant elevation of plasma oxytocin, ACTH, and prolactin levels was 1.0 mg/kg (s.c.), while the minimal dose for corticosterone release was 3.0 mg/kg (s.c.). The ED50 of tandospirone was 1.3 mg/kg for oxytocin, 1.2 mg/kg for ACTH, 3.0 mg/kg for corticosterone, and 0.24 mg/kg for prolactin. Pretreatment with the specific 5-HT1A receptor antagonist WAY 100,635 (0.3 mg/kg, s.c.) completely blocked the effects of tandospirone on plasma levels of oxytocin, ACTH, and corticosterone but shifted the dose-response curve for prolactin to the right. Tandospirone injection (10 mg/kg, s.c.) stimulated the MAP kinase signaling cascade, specifically the phosphorylation of p42/44 extracellular signal-regulated kinase (ERK). Western blot analysis revealed a significant increase in phosphorylated ERK (p-ERK) levels in the hypothalamic paraventricular nucleus (PVN) as well as the dorsal raphe nucleus 5 min following tandospirone injection. These increases were blocked by pretreatment with WAY 100,635 (0.3 mg/kg). The results are the first evidence that systemic 5-HT1A receptor agonist administration produces a rapid increase in p-ERK levels in vivo, providing further insight into the signaling mechanisms of the 5-HT1A receptor.
Keyword Pharmacology & Pharmacy
5-HT1A receptor
MAP kinase
ACTH
Corticosterone
Oxytocin
Prolactin
Dorsal raphe
Paraventricular nucleus
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
 
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Created: Fri, 25 Jan 2008, 16:28:43 EST