Orexin-B Augments Voltage-Gated L-Type Ca2+ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes.

Xu, Ruwei, Roh, Sang-Gun, Gong, Changhong, Hernandez, Maria, Ueta, Yoichi and Chen, Chen (2002) Orexin-B Augments Voltage-Gated L-Type Ca2+ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes.. Neuroendocrinology, 77 3: 141-152. doi:10.1159/000069507


Author Xu, Ruwei
Roh, Sang-Gun
Gong, Changhong
Hernandez, Maria
Ueta, Yoichi
Chen, Chen
Title Orexin-B Augments Voltage-Gated L-Type Ca2+ Current via Protein Kinase C-Mediated Signalling Pathway in Ovine Somatotropes.
Journal name Neuroendocrinology   Check publisher's open access policy
ISSN 0028-3835
Publication date 2002-12-17
Year available 2002
Sub-type Article (original research)
DOI 10.1159/000069507
Volume 77
Issue 3
Start page 141
End page 152
Total pages 12
Place of publication Basel
Publisher Karger
Language eng
Subject 110306 Endocrinology
110201 Cardiology (incl. Cardiovascular Diseases)
111201 Cancer Cell Biology
Abstract Orexins, orexigenic neuropeptides, are secreted from lateral hypothalamus and orexin receptors are expressed in the pituitary. Since growth hormone (GH) secreted from pituitary is integrally linked to energy homeostasis and metabolism, we studied the effect of orexin-B on voltage-gated Ca2+ currents and the related signalling mechanisms in primary cultured ovine somatotropes using whole-cell patch-clamp techniques. With a bath solution containing TEA-Cl (40 mM) and Tetrodotoxin (TTX) (1 µM), three subtypes of Ca2+ currents, namely the long-lasting (L), transient (T), and N currents, were isolated using different holding potentials (-80 and -30 mV) in combination with specific Ca2+ channel blockers (nifedipine and omega-conotoxin). About 75% of the total current amplitude was contributed by the L current, whereas the N and T currents accounted for the rest. Orexin-B (1-100 nM) dose-dependently and reversibly increased only the L current up to approximately 125% of the control value within 4-5 min. Neither a specific protein kinase A (PKA) blocker (H89, 1 µM) nor an inhibitory peptide (PKI, 10 µM) had any effect on the increase in L current by orexin-B. The orexin-B-induced increase in the L current was abolished by concurrent treatment with calphostin C (Cal-C, 100 nM), protein kinase C (PKC) inhibitory peptide (PKC19-36, 1 µM), or by pretreatment with phorbol-12,13-dibutyrate (PDBu) (0.5 µM) for 16 h (a downregulator of PKC). Orexin-B also increased in vitro GH secretion in a dose-dependent manner. We conclude that orexin-B increases the L-type Ca2+ current and GH secretion through orexin receptors and PKC-mediated signalling pathways in ovine somatotropes.
Keyword Orexins
Hypocretin
Ca2+ Channels
Patch clamp
Adenylate-cyclase
Somatotrope
Ovine
Protein kinases
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
 
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Created: Mon, 12 Jan 2009, 15:44:16 EST by Maryanne Watson on behalf of School of Biomedical Sciences