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Endocrine

, Volume 57, Issue 1, pp 179–182 | Cite as

Effects of pasireotide (SOM230) on protein turnover and p70S6 kinase-S6 ribosomal protein signaling pathway in rat skeletal muscle cells

  • Giovanni TulipanoEmail author
  • Lara Faggi
  • Stefan Schulz
  • Maurizio Spinello
  • Andrea Giustina
Research Letter

The multiligand somatostatin (SS-14) analog pasireotide (SOM230) has been approved to treat patients harboring ACTH-secreting pituitary adenomas [1]. The higher binding affinity of pasireotide for the sst5 receptor subtype compared to the first generation analogs, octreotide and lanreotide [2, 3], joint to a functional selectivity of distinct SS-14 analogs at sst2 receptor [4, 5], suggest to explore its potential effects on extra-pituitary tissues. Indeed, SS-14 receptor subtypes (sst1–5) are heterogeneously expressed in different tissues [6]. There is evidence that SS-14 is transiently expressed in motoneurons during early postnatal development in the rat and the expression of sst2, sst3, and sst4 receptor subtypes in rat skeletal muscle decreases progressively during development [7]. To our knowledge, the hypothesis that stable SS-14 analogs may exert some direct effects in skeletal muscle cells has not been tested yet. These effects, if any, would certainly be of interest as to the...

Notes

Acknowledgements

This study was supported by local funds (2012–2013) from the University of Brescia to G.T. and by a grant from Novartis Farma Spa (Origgio, Italy) to the Center for Research in Osteoporosis and Bone Metabolism, University of Brescia (A.G.). Funding sources have not had any role in study design and interpretation of data, except for the personal contribution of the author M.S. which is an employee of Novartis Farma.

Compliance with ethical standards

Conflict of interest

G.T., L.F., declare that they have no conflict of interest. M.S. is employed by Novartis Farma SpA (Origgio, Italy). A.G. has received consulting and lecture fees form Ipsen, Novartis and Pfeizer.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. 1.
    A. Colao, M. Boscaro, D. Ferone, F.F. Casanueva, Managing Cushing’s disease: the state of the art. Endocrine 47, 9–20 (2014)CrossRefGoogle Scholar
  2. 2.
    M. Theodoropoulou, G. Stalla, Somatostatin receptors: from signalling to clinical practice. Front. Neuroendocrinol. 34, 228–252 (2013)CrossRefGoogle Scholar
  3. 3.
    A. Giustina, G. Mazziotti, F. Maffrezzoni, V. Amoroso, A. Berruti, Investigational drugs targeting somatostatin receptors for treatment of acromegaly and neuroendocrine tumors. Expert Opin. Investig. Drugs 23, 1619–1635 (2014)CrossRefGoogle Scholar
  4. 4.
    R. Cescato, K.A. Loesch, B. Waser, H.R. Macke, J.E. Rivier, J.C. Reubi, A. Schonbrunn, Agonist-biased signalling at the sst2A receptor: the multi-somatostatin analogs KE108 and SOM230 activate and antagonize distinct signalling pathways. Mol. Endocrinol. 24, 240–249 (2010)CrossRefGoogle Scholar
  5. 5.
    F. Poll, D. Lehman, S. Illing, M. Ginj, S. Jacobs, A. Lupp, R. Stumm, S. Schulz, Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation. Mol. Endocrinol. 24, 436–446 (2010)CrossRefGoogle Scholar
  6. 6.
    Y.C. Patel, Somatostatin and its receptor family. Front. Neuroendocrinol. 20, 157–198 (1999)CrossRefGoogle Scholar
  7. 7.
    M. Peng, L. Conforto, D.E. Millhorn, Expression of somatostatin receptor genes and acetylcholine receptor development in rat skeletal muscle during postnatal development. Int. J. Mol. Med. 1, 841–848 (1998)PubMedGoogle Scholar
  8. 8.
    G. Tulipano, L. Faggi, A. Cacciamali, M. Spinello, D. Cocchi, A. Giustina, Role of AMP- activated protein kinase activators in antiproliferative multi-drug pituitary tumor therapy: effects of combined treatments with compounds affecting the mTOR-p70S6 kinase axis in cultured pituitary tumor cells. J. Neuroendocrinol. 27, 20–32 (2015)CrossRefGoogle Scholar
  9. 9.
    B. Svejda, M. Kidd, A. Kazberouk, B. Lawrence, R. Pfragner, I.M. Modlin, Limitations in small intestinal neuroendocrine tumor therapy by mTOR kinase inhibition reflect growth factor-mediated PI3K feedback loop activation via ERK1/2 and AKT. Cancer 117, 4141–4154 (2011)CrossRefGoogle Scholar
  10. 10.
    M. Menconi, P. Gonnella, V. Petkova, S. Lecker, P.-O. Hasselgren, Dexamethasone and corticosterone induce similar, but not identical, muscle wasting responses in cultured L6 and C2C12 myotubes. J. Cell Biochem. 105, 353–364 (2008)CrossRefGoogle Scholar
  11. 11.
    G. Tulipano, R. Stumm, M. Pfeiffer, H.J. Kreienkamp, V. Hollt, S. Schulz, Differential trafficking and endosomal sorting of somatostatin receptor subtypes. J. Biol. Chem. 289, 21374–21382 (2004)CrossRefGoogle Scholar
  12. 12.
    G. Tulipano, E. Rossi, M.D. Culler, J.E. Taylor, S. Bonadonna, V. Locatelli, D. Cocchi, A. Giustina, The somatostatin subtype 2 receptor antagonist, BIM-23627, improbe the catabolic effect induced by long-term glucocorticoid treatment in the rat. Regul. Pept. 125, 85–92 (2005)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Giovanni Tulipano
    • 1
    Email author
  • Lara Faggi
    • 1
  • Stefan Schulz
    • 2
  • Maurizio Spinello
    • 3
  • Andrea Giustina
    • 1
    • 4
  1. 1.Department of Molecular and Translational MedicineUniversity of BresciaBresciaItaly
  2. 2.Pharmacology and Toxicology, Jena University GermanyJenaGermany
  3. 3.Novartis Farma SpAOriggioItaly
  4. 4.Endocrine Service, University of BresciaBresciaItaly

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