Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes

Xu, Ruwei, Zhao, Yufeng and Chen, Chen (2002) Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes. The journal of physiology, 545 2: 421-433. doi:10.1113/jphysiol.2002.030916


Author Xu, Ruwei
Zhao, Yufeng
Chen, Chen
Title Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes
Journal name The journal of physiology   Check publisher's open access policy
ISSN 0022-3751
1469-7793
Publication date 2002
Sub-type Article (original research)
DOI 10.1113/jphysiol.2002.030916
Volume 545
Issue 2
Start page 421
End page 433
Total pages 13
Place of publication Oxford
Publisher Blackwell for the Physiological Society
Language eng
Subject 270000 Biological Sciences
320000 Medical and Health Sciences
Abstract Inward-rectifying potassium (Kir) channels are essential for maintaining the resting membrane potential near the K+ equilibrium and they are responsible for hyperpolarisation-induced K+ influx. We characterised the Kir current in primary cultured ovine somatotropes and examined the effect of growth hormone-releasing peptide-2 (GHRP-2) on this current and its related intracellular signalling pathways. The Kir current was, in most cases, isolated using nystatin-perforated patch-clamp techniques. In bath solution containing 5 mM K+, the Kir current was composed of both transient (fast activated) and delayed (slowly activated) components. An increase in the external K+ concentration from 5 to 25 mM induced an augmentation of ~4-fold in the delayed part of the Kir current and both BaCl2 and CsCl dose-dependently inhibited this current, confirming the presence of the Kir current in ovine somatotropes. Moreover, this specific effect of high K+ on the Kir current was only observed in the cells that showed positive staining with anti-growth hormone (GH) antibodies, or in GC cells that belong to a rat somatotrope cell line. Application of GHRP-2 (100 nM) reversibly and significantly reduced the Kir current in bath solutions with 5 or 25 mM K+ in ovine somatotropes. In addition, we found that the reduction in the Kir current mediated by GHRP-2 was totally abolished by the pretreatments with H89 (1 µM) or Rp-cAMP (100 µM) or by intracellular dialysis of a specific protein kinase A (PKA) inhibitory peptide PKI (10 µM). The specific PKC blocker chelerythrine (1 µM) or inhibitory peptide PKC19-36 (10 µM) did not show any effects on the GHRP-2-induced decrease in the Kir current. These results suggest that the inhibition of Kir current through PKA-cAMP pathways may play an integral role in GHRP-2-induced depolarisation and GH release in ovine somatotropes.
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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Citation counts: TR Web of Science Citation Count  Cited 13 times in Thomson Reuters Web of Science Article | Citations
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