Growth hormone promotes Ca2+-induced Ca2+ release in insulin-secreting cells by ryanodine receptor tyrosine phosphorylation

Qimin Zhang, Martin Köhler, Shao Nian Yang, Fan Zhang, Olof Larsson, Per Olof Berggren

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Elevation in cytoplasmic free Ca2+ concentration ([Ca 2+]i) is a common mechanism in signaling events. An increased [Ca2+]i induced by GH, has been observed in relation to different cellular events. Little is known about the mechanism underlying the GH effect on Ca2+ handling. We have studied the molecular mechanisms underlying GH-induced rise in [Ca2+]i in BRIN-BD11 insulin-secreting cells. GH (500 ng/ml, 22 nM) induced a sustained increase in [Ca2+]i. The effect of GH on [Ca 2+]i was prevented in the absence of extracellular Ca 2+ and was inhibited by the ATP-sensitive K+-channel opener diazoxide and the voltage-dependent Ca2+-channel inhibitor nifedipine. However, GH failed to induce any changes in Ca2+ current and membrane potential, evaluated by patch-clamp recordings and by using voltage-sensitive dyes. When the intracellular Ca2+ pools had been depleted using the Ca2+-ATPase inhibitor thapsigargin, the effect of GH was inhibited. In addition, GH-stimulated rise in [Ca2+] i was completely abolished by ruthenium red, an inhibitor of mitochondrial Ca2+ transport, and caffeine. GH induced tyrosine phosphorylation of ryanodine receptors. The effect of GH on [Ca 2+]i was completely blocked by the tyrosine kinase inhibitors genistein and lavendustin A. Interestingly, treatment of the cells with GH significantly enhanced K+-induced rise in [Ca 2+]i. Hence, GH-stimulated rise in [Ca2+] i is dependent on extracellular Ca2+ and is mediated by Ca2+-induced Ca2+ release. This process is mediated by tyrosine phosphorylation of ryanodine receptors and may play a crucial rale in physiological Ca2+ handling in insulin-secreting cells.

Original languageEnglish
Pages (from-to)1658-1669
Number of pages12
JournalMolecular Endocrinology
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

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Ryanodine Receptor Calcium Release Channel
Insulin-Secreting Cells
Growth Hormone
Tyrosine
Phosphorylation
Diazoxide
Ruthenium Red
Thapsigargin
Calcium-Transporting ATPases
Genistein
Respiratory Sounds
Nifedipine
Caffeine
Membrane Potentials
Protein-Tyrosine Kinases
Coloring Agents
Adenosine Triphosphate
lavendustin A

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Growth hormone promotes Ca2+-induced Ca2+ release in insulin-secreting cells by ryanodine receptor tyrosine phosphorylation. / Zhang, Qimin; Köhler, Martin; Yang, Shao Nian; Zhang, Fan; Larsson, Olof; Berggren, Per Olof.

In: Molecular Endocrinology, Vol. 18, No. 7, 01.07.2004, p. 1658-1669.

Research output: Contribution to journalArticle

Zhang, Qimin ; Köhler, Martin ; Yang, Shao Nian ; Zhang, Fan ; Larsson, Olof ; Berggren, Per Olof. / Growth hormone promotes Ca2+-induced Ca2+ release in insulin-secreting cells by ryanodine receptor tyrosine phosphorylation. In: Molecular Endocrinology. 2004 ; Vol. 18, No. 7. pp. 1658-1669.
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