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Companion Animals Models of Human Disease
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
The prevalence of GH (growth hormone)-secreting pituitary tumors in domestic cats (Felis catus) is ten-fold greater than in humans. The predominant inhibitory receptors of GH-secreting pituitary tumors are somatostatin receptors (SSTRs) and D2 dopamine receptors (DRD2). The expression of these receptors is associated with the response to somatostatin analog and dopamine agonist treatment in human patients with acromegaly. A study in cats evaluated pathological features of pituitaries from domestic cats with acromegaly, pituitary receptor expression, and investigated correlates with clinical data, including pituitary volume, time since diagnosis of diabetes, insulin requirement, and serum IGF1 concentration. Loss of reticulin structure was identified in 15 of 21 pituitaries, of which 10 of 15 exhibited acinar hyperplasia. SSTR1, SSTR2, SSTR5, and DRD2 mRNA were identified in the feline pituitary, whereas SSTR3 and SSTR4 were not. Expression of SSTR1, SSTR2, and SSTR5 was greater in acromegalic cats compared with controls. A negative correlation was identified between DRD2 mRNA expression and pituitary volume(24,25).
Radiolabeled Agents for Molecular Imaging and/or Therapy
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
Dimitrios Psimadas, Eirini A. Fragogeorgi
All somatostatin analogs mentioned earlier are agonists that induce receptor internalization. However, high-affinity sstr2- and sstr3-selective SST antagonists can perform as well as or even better than agonists in terms of in vivo uptake in corresponding tumor xenografts, despite their poor internalization (Ginj et al. 2006).
Radionuclide imaging of carcinoid tumors, neurendocrine tumors of the pancreas and adrenals
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Technetium-labeled investigational somatostatin analogs have also been investigated with favorable results in GEPNETs, and these included 99mTc-depreotide, which binds with high affinity to SSTR2, SSTR3, and SSTR5; 99mTc-vapreotide, which binds with high affinity to SSTR2 and SSTR5 and, to a lesser extent, SSTR3 and SSTR4; 99mTc-HYNIC-TOC; and 99mTc-HYNIC-[Tyr3,Thr8]-octreotide (TATE) [29, 65, 72]. There are advantages of 99mTc-labeled somatostatin analogs over 111In-DTPA-octreotide imparted by superior imaging capabilities of the extrahepatic metastases and better individual separation of lesions. However, these results should be analyzed with caution since most of these reported comparisons did not use the optimal imaging protocols for 111In-DTPA-octreotide SRS defined by the European and U.S. guidelines [20–23].
Cluster headache therapies: pharmacology and mode of action
Published in Expert Review of Clinical Pharmacology, 2020
Jasper Mecklenburg, Margarita Sanchez Del Rio, Uwe Reuter
While negative trial results of SOM230 suggest a lack of efficacy of somatostatin agonists, octreotide has additional effects on SST2 and SST3. Nevertheless, at this stage, octreotide is only an experimental drug in CH therapy. The absence of vascular side effects could render this drug an alternative for patients with vascular risk factors who do not respond to oxygen under the condition that a clinical trial with octreotide proves efficacy of the substance.
SSTR2 associated with neuronal apoptosis after intracerebral hemorrhage in adult rats
Published in Neurological Research, 2018
Xiang Tan, Shuyao Wang, Changyun Guo, Min Qian, Xinli Zhang, Peng Wan, Chao Yu, Baojian Geng, Kaifu Ke, Jiabing Shen, Yan Song, Min Yu
SST exerts several important physiological actions to modulate neurotransmission, cell secretion, and cell proliferation in the adult central nervous system through interactions with SST receptors 1-5 (SSTR1-5), encoded by separate genes [20–22]. Cloned SSTR2 has been reported to inhibit Ca2+ conductance when expressed in RINm5F cells [23]. Studies over the last few years show that SST and its receptors appear to play an important role in cell death in mice. In a retina ischemia model, activation of the SSTR2 protected retinal neurons from damage [24]. In the pituitary tumor cells the octreotid, a SST analog, mediates its anti-proliferative action by altering phosphatidylinositol-3-kinase (PI3K)-Akt signaling [25]. Also in neuroendocrine tumors octreotid decreases PI3K-Akt signaling [26]. Deletion of SSTR2 results in a selective, global and progressive noradrenergic axonal degeneration [27]. SSTR2 may also play a crucial role as a local inhibitor of FSH action on GCs apoptosis and steroidogenesis [13]. Findings indicate a new role for SSTR2 in modulation of signaling pathways involved in cancer progression and provide novel therapeutic approaches in breast cancer treatment, and that may be associated to (PI3K)/AKT signal way [28]. SSTR2 expression induced an executioner caspase-mediated apoptosis through a tyrosine phosphatase SHP-1 (Src homology domain phosphatase-1)-dependent stimulation of nuclear factor kappa B (NF-κB) activity and subsequent inhibition of the mitogenactivated protein kinase JNK [29]. Additionally, Bodmer D, et al. reported that pasireotide (an SST analog) binding to SSTR2, prevented gentamicin-induced hair cells death through a nuclear translocation of the Ca2+-sensitive transcription factor, nuclear factor of activated T cells (NFAT) in the mouse organ of Corti [30]. Recently, SSTR1 and SSTR3 were reported to associate with neuronal apoptosis after ICH, and the mechanism are not claimed [31,32]. As an SST receptor, SSTR2 differed from SSTR1 and SSTR3 in its mechanism of action, the three of them having a negative role for neurological functions [10]. However, increased expression of SSTR2 might inactivate SSTR3 functions following heterodimerization, its true relationship between the pathology of ICH are not clear [12,27]. Nevertheless, the actions of SST are mediated by its five distinct subtypes, while its self-variations are still not clear yet.