Up-regulation of high voltage-activated Ca(2+) channels in GC somatotropes after long-term exposure to ghrelin and growth hormone releasing peptide-6.
(2008)
Journal - Cellular and molecular neurobiology (United States )
Abstract :
Activation of the growth hormone (GH)-secretagogue receptor (GHS-R) by synthetic GH-releasing peptides (GHRP) or its endogenous ligand (ghrelin) stimulates GH release. Though much is known about the signal transduction underlying short-term regulation, there is far less information on mechanisms that produce long-term effects. In the current report, using whole-cell patch-clamp recordings, we assessed the long-term actions of such regulatory factors on voltage-activated Ca(2+) currents in GH-secreting cells derived from a rat pituitary tumour (GC cell line). After 96 h in culture, all recorded GC somatotropes exhibited two main Ca(2+) currents: a medium voltage-activated (MVA; T/R-type) and a high voltage-activated (HVA; mostly dihydropyridine-sensitive L-type) current. Interestingly, L- and non-L-type channels were differentially up-regulated by GHRP-6 and ghrelin. Chronic treatment with the GHS induced a significant selective increase on Ba(2+) current through HVA Ca(2+) channels, and caused only a modest increase of currents through MVA channels. Consistent with this, in presence of D-(Lys(3))-GHRP-6, a specific antagonist of the GHS-R, the increase in HVA Ca(2+) channel activity after chronic treatment with the GHS was abolished. The stimulatory effect on HVA current density evoked by the secretagogues was accompanied by an augment in maximal conductance with no apparent changes in the kinetics and the voltage dependence of the Ca(2+) currents, suggesting an increase in the number of functional channels in the cell membrane. Lastly, in consistency with the functional data, quantitative real-time RT-PCR revealed that the expression level of transcripts encoding for the Ca(V)1.3 pore-forming subunit of the L-type channels was significantly increased after chronic treatment of the GC cells with ghrelin.
| ISSN : | 0272-4340 |
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| Mesh Heading : | Animals Calcium Channels Calcium Channels, L-Type Cell Line, Tumor Ghrelin Ion Channel Gating Oligopeptides Patch-Clamp Techniques Rats Receptors, Ghrelin Somatotrophs Up-Regulation biosynthesis pharmacology |
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| Mesh Heading Relevant : | biosynthesis physiology pharmacology agonists metabolism |
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Ghrelin and GHRP-6 enhance electrical and secretory activity in GC somatotropes.
(2007)
Journal - Biochemical and biophysical research communications (United States )
Abstract :
It is well established that pituitary somatotropes fire spontaneous action potentials (SAP) which generate Ca(2+) signals of sufficient amplitude to trigger growth hormone (GH) release. It is also known that ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate GH secretion, though the mechanisms involved remain unclear. In the current report, we show that the chronic (96h) treatment with ghrelin and GHRP-6 increases the firing frequency of SAP in the somatotrope GC cell line. This action is associated with a significant increase in whole-cell inward current density. In addition, long-term application of Na(+) or L-type Ca(2+) current antagonists decreases GHRP-6-induced release of GH, indicating that the ionic currents that give rise to SAP play important roles for hormone secretion in the GC cells. Together, our results suggest that ghrelin and GHPR-6 may increase whole-cell inward current density thereby enhancing SAP firing frequency and facilitating GH secretion from GC somatotropes.
| ISSN : | 0006-291X |
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| Mesh Heading : | 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester Action Potentials Animals Calcium Channel Agonists Calcium Channel Blockers Cell Line Cell Line, Tumor Ghrelin Growth Hormone Ion Channel Gating Nifedipine Oligopeptides Patch-Clamp Techniques Peptide Hormones Pituitary Neoplasms Rats Receptors, Somatotropin Somatotrophs pharmacology pharmacology pharmacology pharmacology metabolism physiology |
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| Mesh Heading Relevant : | drug effects secretion pharmacology pharmacology drug effects |
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