Somatostatin acts by inhibiting the cyclic 3',5'-adenosine monophosphate (cAMP)/protein kinase A pathway, cAMP response element-binding protein (CREB) phosphorylation, and CREB transcription potency

Molecular Endocrinology
J J TentlerA Gutierrez-Hartmann

Abstract

Somatostatin (SRIF) was discovered as an inhibitor of GH secretion from pituitary somatotroph cells. SRIF analogs are very effective agents used to treat neuroendocrine tumors and are now being used with increasing frequency in clinical trials to treat more aggressive malignancies. However, the cellular components mediating SRIF signal transduction remain largely unknown. We have stably overexpressed the SRIF type 2 receptor (SST2) in GH4 rat somatomammotroph cells, establishing a physiologically relevant model system. In this model, the SRIF analog, BIM23014, inhibited forskolin-induced cAMP accumulation, protein kinase A activation, cAMP response element-binding protein phosphorylation, and Pit-1/GHF-1 promoter activation in an okadaic acid-insensitive manner. Pertussis toxin inhibited the effects of BIM23014, documenting that SST2 signaling was coupled to Gi. Moreover, the inhibitory effects of BIM23014 were reversed by overexpression of protein kinase A catalytic subunit, indicating that SRIF does not act via serine/threonine phosphatases, but, rather, by lowering protein kinase A activity. These data define the components of the SRIF/SST2 receptor signaling pathway and provide important mechanistic insights into how SRIF c...Continue Reading

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Citations

Mar 13, 2014·Molecular Endocrinology·Tamar EiglerShlomo Melmed
Oct 3, 2002·Biochemical and Biophysical Research Communications·Maria C ZatelliEttori C degli Uberti
Nov 5, 2013·Trends in Pharmacological Sciences·Jean Claude Reubi, Agnes Schonbrunn
Jul 23, 2013·Frontiers in Neuroendocrinology·Marily Theodoropoulou, Günter K Stalla
Dec 29, 2012·Trends in Endocrinology and Metabolism : TEM·Mônica R GadelhaMárta Korbonits
Jan 16, 2009·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Naoki Hattori
May 21, 2011·Clinical and Experimental Pharmacology & Physiology·Jun WangYan Zhao
Mar 11, 2011·Annals of the New York Academy of Sciences·Thomas CunyAlain Enjalbert
Apr 3, 2012·International Journal of Cardiology·Rishi K SomvanshiUjendra Kumar
May 11, 2001·Neuropeptides·Z Csaba, P Dournaud
Feb 13, 2010·Trends in Endocrinology and Metabolism : TEM·Anat Ben-Shlomo, Shlomo Melmed
Dec 14, 2007·Developmental Neuroscience·Yulan JiangHitoshi Komuro

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