全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Potassium Current Is Not Affected by Long-Term Exposure to Ghrelin or GHRP-6 in Somatotropes GC Cells

DOI: 10.1155/2013/913792

Full-Text   Cite this paper   Add to My Lib

Abstract:

Ghrelin is a growth hormone (GH) secretagogue (GHS) and GHRP-6 is a synthetic peptide analogue; both act through the GHS receptor. GH secretion depends directly on the intracellular concentration of Ca2+; this is determined from the intracellular reserves and by the entrance of Ca2+ through the voltage-dependent calcium channels, which are activated by the membrane depolarization. Membrane potential is mainly determined by K+ channels. In the present work, we investigated the effect of ghrelin (10?nM) or GHRP-6 (100?nM) for 96?h on functional expression of voltage-dependent K+ channels in rat somatotropes: GC cell line. Physiological patch-clamp whole-cell recording was used to register the K+ currents. With Cd2+ (1?mM) and tetrodotoxin (1?μm) in the bath solution recording, three types of currents were characterized on the basis of their biophysical and pharmacological properties. GC cells showed a K+ current with a transitory component sensitive to 4-aminopyridine, which represents ~40% of the total outgoing current; a sustained component named delayed rectifier , sensitive to tetraethylammonium; and a third type of K+ current was recorded at potentials more negative than ?80?mV, permitting the entrance of K+ named inward rectifier (KIR). Chronic treatment with ghrelin or GHRP-6 did not modify the functional expression of K+ channels, without significant changes ( ) in the amplitudes of the three currents observed; in addition, there were no modifications in their biophysical properties and kinetic activation or inactivation. 1. Introduction The growth hormone is mainly under the control of two hypothalamic neuropeptides acting in opposition: one, the growth hormone releasing hormone (GHRH), as a stimulant, and the other, somatostatin, as an inhibitor [1, 2]. The GHRH specifically bind to its receptor on the plasmatic membrane of the somatotropes; this increments the activity of adenylate cyclase, which increases the generation of AMPc [3, 4]. This increase in the AMPc levels let to open the voltage-dependent Ca2+ channels [5, 6] and a rapid increase in the intracellular Ca2+ concentration [Ca2+], thus promoting the exocytosis of GH [7, 8]. The inhibitory effect of somatostatin involves the inhibition of adenylate cyclase activity and a reduction of [9, 10]. In addition to the GHRH, a group of synthetic oligopeptides releasing GH (GHRPs) or GH secretagogues (GHS) are capable of stimulating the secretion of GH [2, 11, 12]. The GH-releasing peptide-6 (GHRP-6) is one of the most representative of those compounds [2, 11–13]. Research on the mechanism of

References

[1]  M. T. Bluet-Pajot, V. Tolle, P. Zizzari et al., “Growth hormone secretagogues and hypothalamic networks,” Endocrine, vol. 14, no. 1, pp. 1–8, 2001.
[2]  A. W. Root and M. J. Root, “Clinical pharmacology of human growth hormone and its secretagogues,” Current Drug Targets, vol. 2, no. 1, pp. 27–52, 2002.
[3]  A. O. L. Wong, B. C. Moor, C. E. Hawkins, N. Narayanan, and J. Kraicer, “Cytosolic protein kinase A mediates the growth hormone (GH)-releasing action of GH-releasing factor in purified rat somatotrophs,” Neuroendocrinology, vol. 61, no. 5, pp. 590–600, 1995.
[4]  M. M. Malagón, R. M. Luque, E. Ruiz-Guerrero et al., “Intracellular Signaling Mechanisms Mediating Ghrelin-Stimulated Growth Hormone Release in Somatotropes,” Endocrinology, vol. 144, no. 12, pp. 5372–5380, 2003.
[5]  M. Kato and M. Suzuki, “Inhibition by nimodipine of growth hormone (GH) releasing factor-induced GH secretion from rat anterior pituitary cells,” Japanese Journal of Physiology, vol. 41, no. 1, pp. 63–74, 1991.
[6]  A. P. Naumov, J. Herrington, and B. Hille, “Actions of growth-hormone-releasing hormone on rat pituitary cells: intracellular calcium and ionic currents,” Pflugers Archiv European Journal of Physiology, vol. 427, no. 5-6, pp. 414–421, 1994.
[7]  R. W. Holl, M. O. Thorner, G. L. Mandell, J. A. Sullivan, Y. N. Sinha, and D. A. Leong, “Spontaneous oscillations of intracellular calcium and growth hormone secretion,” Journal of Biological Chemistry, vol. 263, no. 20, pp. 9682–9685, 1988.
[8]  M. O. Thorner, R. W. Holl, and D. A. Leong, “The somatotrope: a endocrine cell with functional calcium transients,” Journal of Experimental Biology, vol. 139, pp. 169–179, 1988.
[9]  M. J. Cronin, S. T. Summers, M. A. Sortino, and E. L. Hewlett, “Protein kinase C enhances growth hormone releasing factor (1-40)-stimulated cyclic AMP levels in anterior pituitary. Actions of somatostatin and pertussis toxin,” Journal of Biological Chemistry, vol. 261, no. 30, pp. 13932–13935, 1986.
[10]  D. L. Lewis, F. F. Weight, and A. Luini, “A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium current by somatostatin in a pituitary cell line,” Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 23, pp. 9035–9039, 1986.
[11]  C. Chen, “Growth hormone secretagogue actions on the pituitary gland: multiple receptors for multiple ligands?” Clinical and Experimental Pharmacology and Physiology, vol. 27, no. 5-6, pp. 323–329, 2000.
[12]  R. G. Smith, “Development of growth hormone secretagogues,” Endocrinology Review, vol. 26, no. 3, pp. 346–360, 2005.
[13]  C. Y. Bowers, F. A. Momany, G. A. Reynolds, and A. Hong, “On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone,” Endocrinology, vol. 114, no. 5, pp. 1537–1545, 1984.
[14]  M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, and K. Kangawa, “Ghrelin is a growth-hormone-releasing acylated peptide from stomach,” Nature, vol. 402, no. 6762, pp. 656–660, 1999.
[15]  R. Xu, Y. Zhao, and C. Chen, “Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatoropes,” Journal of Physiology, vol. 545, no. 2, pp. 421–433, 2002.
[16]  J. Herrington and B. Hille, “Growth hormone-releasing hexapeptide elevates intracellular calcium in rat somatotropes by two mechanisms,” Endocrinology, vol. 135, no. 3, pp. 1100–1108, 1994.
[17]  S. M. Simasko, “A background sodium conductance is necessary for spontaneous depolarizations in rat pituitary cell line GH3,” American Journal of Physiology-Cell Physiology, vol. 266, no. 3, pp. C709–C719, 1994.
[18]  S. M. Sims, B. T. Lussier, and J. Kraicer, “Somatostatin activates an inwardly rectifying K+ conductance in freshly dispersed rat somatotrophs,” Journal of Physiology, vol. 441, pp. 615–637, 1991.
[19]  C. Chen, “Gi-3 protein mediates the increase in voltage-gated K+ currents by somatostatin on cultured ovine somatotropes,” American Journal of Physiology, vol. 275, part 1, no. 2, pp. E278–E284, 1998.
[20]  F. H. Xue, L. Z. Yun, M. Hernandez, D. J. Keating, and C. Chen, “Ghrelin reduces voltage-gated potassium currents in GH3 cells via cyclic GMP pathways,” Endocrine, vol. 28, no. 2, pp. 217–224, 2005.
[21]  B. Dominguez, R. Felix, and E. Monjaraz, “Ghrelin and GHRP-6 enhance electrical and secretory activity in GC somatotropes,” Biochemical and Biophysical Research Communications, vol. 358, no. 1, pp. 59–65, 2007.
[22]  A. Marty and E. Neher, “Tight-seal whole-cell recording,” in Single-Channel Recording, B. Sakmann and E. Neher, Eds., pp. 31–52, Plenum Press, New York, NY, USA, 1995.
[23]  G. Avila, A. Sandoval, and R. Felix, “Intramembrane charge movement associated with endogenous K+ channel activity in HEK-293 cells,” Cellular and Molecular Neurobiology, vol. 24, no. 3, pp. 317–330, 2004.
[24]  L. A. Frohman, T. R. Downs, and P. Chomczynski, “Regulation of growth hormone secretion,” Frontiers in Neuroendocrinology, vol. 13, no. 4, pp. 344–405, 1992.
[25]  M. Yamazaki, H. Kobayashi, T. Tanaka, K. Kangawa, K. Inoue, and T. Sakai, “Ghrelin-induced growth hormone release from isolated rat anterior pituitary cells depends on intracellular and extracellular Ca2+ sources,” Journal of Neuroendocrinology, vol. 16, no. 10, pp. 825–831, 2004.
[26]  B. Dominguez, T. Avila, J. Flores-Hernandez et al., “Up-regulation of high voltage-activated Ca2+ channels in GC somatotropes after long-term exposure to ghrelin and growth hormone releasing peptide-6,” Cellular and Molecular Neurobiology, vol. 28, no. 6, pp. 819–831, 2008.
[27]  B. Dominguez, R. Felix, and E. Monjaraz, “Upregulation of voltage-gated Na+ channels by long-term activation of the ghrelin-growth hormone secretagogue receptor in clonal GC somatotropes,” American Journal of Physiology-Endocrinology and Metabolism, vol. 296, no. 5, pp. E1148–E1156, 2009.
[28]  X. Han, Y. Zhu, Y. Zhao, and C. Chen, “Ghrelin reduces voltage-gated calcium currents in GH3 cells via cyclic GMP pathways,” Endocrine, vol. 40, no. 2, pp. 228–236, 2011.
[29]  F. Van Goor, D. Zivadinovic, and S. S. Stojilkovic, “Differential expression of ionic channels in rat anterior pituitary cells,” Molecular Endocrinology, vol. 15, no. 7, pp. 1222–1236, 2001.
[30]  J. Herrington and C. J. Lingle, “Multiple components of voltage-dependent potassium current in normal rat anterior pituitary cells,” Journal of Neurophysiology, vol. 72, no. 2, pp. 719–729, 1994.
[31]  S. S. Stojilkovic, J. Tabak, and R. Bertram, “Ion channels and signaling in the pituitary gland,” Endocrine Reviews, vol. 31, no. 6, pp. 845–915, 2010.
[32]  C. Chen, P. Heyward, J. Zhang, D. Wu, and I. J. Clarke, “Voltage-dependent potassium currents in ovine somatotrophs and their function in growth hormone secretion,” Neuroendocrinology, vol. 59, no. 1, pp. 1–9, 1994.
[33]  S. Sankaranarayanan and S. M. Simasko, “Potassium channel blockers have minimal effect on repolarization of spontaneous action potentials in rat pituitary lactotropes,” Neuroendocrinology, vol. 68, no. 5, pp. 297–311, 1998.
[34]  A. C. Charles, E. T. Piros, C. J. Evans, and T. G. Hales, “L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH3 cells,” Journal of Biological Chemistry, vol. 274, no. 11, pp. 7508–7515, 1999.
[35]  C. Chen, J. Zhang, J. D. Vincent, and J. M. Israel, “Somatostatin increases voltage-dependent potassium currents in rat somatotropes,” American Journal of Physiology, vol. 259, no. 6, part 1, pp. C854–C861, 1990.
[36]  K. Takano, J. Yasufuku-Takano, A. Teramoto, and T. Fujita, “G(i3) mediates somatostatin-induced activation of an inwardly rectifying K+ current in human growth hormone-secreting adenoma cells,” Endocrinology, vol. 138, no. 6, pp. 2405–2409, 1997.
[37]  R. Xu, S. G. Roh, K. Loneragan, M. Pullar, and C. Chen, “Human GHRH reduces voltage-gated K+ currents via a non-cAMP-dependent but PKC-mediated pathway in human GH adenoma cells,” Journal of Physiology, vol. 520, no. 3, pp. 697–707, 1999.
[38]  R. Xu, I. J. Clarke, S. Chen, and C. Chen, “Growth hormone-releasing hormone decreases voltage-gated potassium currents in GH4C1 cells,” Journal of Neuroendocrinology, vol. 12, no. 2, pp. 147–157, 2000.
[39]  J. F. McGurk, S. S. Pong, L. Y. Chaung, M. Gall, B. Butler, and J. P. Arena, “Growth hormone secretagogues modulate potassium currents in rat somatotropes,” in Proceedings of the 23rd Annual Meeting of Society for Neurosciences, 1993, Abstract 642. 1.
[40]  C. Chen, “The effect of two-day treatment of primary cultured ovine somatotropes with GHRP-2 on membrane voltage-gated K+ currents,” Endocrinology, vol. 143, no. 7, pp. 2659–2663, 2002.
[41]  Z. Peng, Z. Xiaolei, H. Al-Sanaban, X. Chengrui, and Y. Shengyi, “Ghrelin inhibits insulin release by regulating the expression of inwardly rectifying potassium channel 6. 2 in islets,” American Journal Medical Science, vol. 343, no. 3, pp. 215–219, 2012.
[42]  D. Bajic, Q. V. Hoang, S. Nakajima, and Y. Nakajima, “Dissociated histaminergic neuron cultures from the tuberomammillary nucleus of rats: culture methods and ghrelin effects,” Journal of Neuroscience Methods, vol. 132, no. 2, pp. 177–184, 2004.
[43]  M. Korbonits, S. A. Bustin, M. Kojima et al., “The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 2, pp. 881–887, 2001.
[44]  C. K. Bauer, I. Davison, I. Kubasov, J. R. Schwarz, and W. T. Mason, “Different G proteins are involved in the biphasic response of clonal rat pituitary cells to thyrotropin-releasing hormone,” Pflugers Archiv European Journal of Physiology, vol. 428, no. 1, pp. 17–25, 1994.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133