Orexin-A Augments Voltage-Gated Ca2 Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes

Xu, Ruwei, Wang, Qinling, Yan, Ming, Hernandez, Maria, Gong, Chang-Hong, Boon, Wah-Chin, Murata, Yoko, Ueta, Yoichi and Chen, Chen (2002) Orexin-A Augments Voltage-Gated Ca2 Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes. Endocrinology, 143 12: 4609-4619. doi:10.1210/en.2002-220506


Author Xu, Ruwei
Wang, Qinling
Yan, Ming
Hernandez, Maria
Gong, Chang-Hong
Boon, Wah-Chin
Murata, Yoko
Ueta, Yoichi
Chen, Chen
Title Orexin-A Augments Voltage-Gated Ca2 Currents and Synergistically Increases Growth Hormone (GH) Secretion with GH-Releasing Hormone in Primary Cultured Ovine Somatotropes
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
Publication date 2002-01-01
Year available 2002
Sub-type Article (original research)
DOI 10.1210/en.2002-220506
Volume 143
Issue 12
Start page 4609
End page 4619
Total pages 11
Place of publication Bethesda, MA
Publisher Endocrine Society
Collection year 2002
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
111201 Cancer Cell Biology
Abstract Orexins are recently discovered neuropeptides that play an important role in the regulation of hormone secretion, and their receptors have been recently demonstrated in the pituitary. The effects of orexin-A on voltage-gated Ca2 currents and GH release in primary cultured ovine somatotropes were examined. The expression of orexin-1 receptor was demonstrated by RT-PCR in ovine somatotropes, from which Ca2 currents were also isolated as L, T, and N currents. Application of orexin-A (100 nM) significantly and reversibly increased only the L current, and coadministration of orexin-A and GHRH (10 nM) showed an additive effect on this current, but no effect of orexin-A was observed on eitherTorNcurrent. Furthermore, the orexin-A-induced increase in the L current was completely abolished by the inhibition of protein kinase C (PKC) activity using calphostin C (100 nM), phorbal 12,13- dibutyrate pretreatment (0.5 M) for 16 h or specific PKC inhibitory peptide PKC19–36 (1 mM). However, the increase in L current by orexin-A was sustained when cells were preincubated with a specific protein kinase A blocker H89 (1 M) or a specific intracellular Ca2 store depleting reagent thapsigargin (1 M). Finally, orexin-A alone did not significantly increase GH release, but coadministration of orexin-A and GHRH showed a synergistic effect on GH secretion in vitro. Our results therefore suggest that orexin-A may play an important role in regulating GHRH-stimulated GH secretion through the enhancement of the L-type Ca2 current and the PKC-mediated signaling pathway in ovine somatotropes. (Endocrinology 143: 4609–4619, 2002)
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 40 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 12 Jan 2009, 23:48:49 EST by Maryanne Watson on behalf of School of Biomedical Sciences