Somatostatin inhibits exocytosis in rat pancreatic α‐cells by Gi2‐dependent activation of calcineurin and depriming of secretory granules
| العنوان: | Somatostatin inhibits exocytosis in rat pancreatic α‐cells by Gi2‐dependent activation of calcineurin and depriming of secretory granules |
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| المؤلفون: | Marianne Høy, Patrik Rorsman, Jesper Gromada, Karsten Buschard, Albert Salehi |
| المصدر: | The Journal of Physiology. 535:519-532 |
| بيانات النشر: | Wiley, 2001. |
| سنة النشر: | 2001 |
| مصطلحات موضوعية: | Male, Cytoplasm, endocrine system, medicine.medical_specialty, Patch-Clamp Techniques, Calcium Channels, L-Type, Nifedipine, Physiology, GTP-Binding Protein alpha Subunits, Gi-Go, Biology, Glucagon, Exocytosis, Membrane Potentials, Islets of Langerhans, Adenosine Triphosphate, Calcium Channels, N-Type, omega-Conotoxin GVIA, Proto-Oncogene Proteins, Internal medicine, medicine, Animals, Secretion, Protein kinase A, Delta cell, Somatostatin receptor, Calcineurin, Secretory Vesicles, Colforsin, Glucagon secretion, Original Articles, Calcium Channel Blockers, Phosphoric Monoester Hydrolases, Rats, Somatostatin, Endocrinology, Rats, Inbred Lew, Calcium, GTP-Binding Protein alpha Subunit, Gi2, Oligoribonucleotides, Antisense |
| الوصف: | The hormone glucagon is secreted from pancreatic α-cells during hypoglycaemia. Hormones and neurotransmitters such as adrenaline and somatostatin, which stimulate and inhibit glucagon release, respectively, modulate the release of the glucagon. Somatostatin is produced and secreted from the δ-cells, which are juxtaposed to the α-cells in the outer part of the islet of Langerhans (Gopel et al. 2000). This paracrine regulation of glucagon secretion is principally mediated by somatostatin receptors of the SSTR2-subtype (Kuman et al. 1999; Strowski et al. 2000) and is believed to involve several mechanisms. First, it suppresses α-cell electrical activity by activation of a sulphonylurea-insensitive low-conductance K+ channel (Yoshimoto et al. 1999; Gromada et al. 2001). Second, somatostatin inhibits cyclic AMP production and thus reduces protein kinase A-dependent secretion (Fehmann et al. 1995). Third, somatostatin suppresses Ca2+-dependent exocytosis by a mechanism exerted distally to the elevation of cytoplasmic Ca2+ concentration (Ding et al. 1997). The molecular mechanisms by which somatostatin modulates exocytosis in the α-cells remain largely unestablished. There is evidence that the secretory granules in the α-cell, by analogy to what is the case in other neuroendocrine cells, can be functionally subdivided into a reserve pool and a readily releasable pool (RRP). Most of the granules belong to the reserve pool and only ∼100 are immediately available for release (Gromada et al. 1997). The process by which the granules go from the reserve pool to the RRP (mobilisation) is poorly characterised in α-cells but is accelerated by agents that activate protein kinase A (Gromada et al. 1997). In β-cells (Vallar et al. 1987; Eliasson et al. 1997) as well as pituitary melanotrophs (Parsons et al. 1995) and adrenal chromaffin cells (Holz et al. 1989) there is also evidence that ATP hydrolysis (priming) is required for the granules to attain release competence. Whether this is also the case in the α-cell is unclear. It is likewise unknown whether granules that have already been primed can lose their release competence by depriming. Here we have used high-resolution capacitance measurements to explore the mechanisms by which somatostatin suppresses exocytosis in single rat pancreatic α-cells. We demonstrate that the secretory granules become release competent by ATP-dependent priming and that somatostatin inhibits exocytosis by Gi2-dependent activation of the protein phosphatase calcineurin. Evidence is also provided that somatostatin acts by selectively depriming granules associated with L-type Ca2+ channels whereas exocytosis of granules close to N-type Ca2+ channels is unaffected, suggesting that somatostatin receptors may exclusively locate to the L-type Ca2+ channels. |
| تدمد: | 1469-7793 0022-3751 |
| DOI: | 10.1111/j.1469-7793.2001.00519.x |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79d85afbf28931904c9b12e8dd4a4e6c https://doi.org/10.1111/j.1469-7793.2001.00519.x |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....79d85afbf28931904c9b12e8dd4a4e6c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14697793 00223751 |
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| DOI: | 10.1111/j.1469-7793.2001.00519.x |