Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors

Although in situ hybridization has been used to examine the distribution of messenger RNA for somatostatin receptor subtypes (sst) in human tumors, the cellular localization of sst1 and sst2A receptors has not been reported. In this study, we describe the cellular localization of human sst1 and sst2A receptor proteins in both cryostat- and paraffin-embedded sections of 25 human tumor tissues using two recently developed polyclonal antibodies. Six somatostatin (SS) receptor (SSR) positive tumors (two gastrinomas, three carcinoids, one pheochromocytoma) and one SSR negative tumor (renal cell carcinoma), selected by positive and negative SSR autoradiography, respectively, were studied by both immunohistochemistry and Western blot analysis. The six SSR positive tumors expressed sst2A, while 4 of 5 expressed sst1 as well. The SSR negative tumor did not express either sst1 or sst2A. Western blot analysis of wheat germ agglutinin purified membrane proteins confirmed the presence of the sst1 and sst2A glycosylated receptors. The paraffin-embedded sections gave best information with respect to the subcellular localization. Sst1 immunoreactivity was observed both on the membrane and in the cytoplasm, while sst2A showed predominantly membrane-associated immunoreactivity. This subcellular distribution of sst1 or sst2A receptors was confirmed in paraffin-embedded sections of 8 additional intestinal carcinoids, 5 gastrinomas and 5 pheochromocytomas. Sst1 receptors were detected in 7 out of 8 carcinoids, in all gastrinomas, and in 4 out of 5 pheochromocytomas, while 6 out of 8 carcinoids, all gastrinomas, and 3 out of 5 pheochromocytomas expressed sst2A receptors. In conclusion, sst1 and sst2A receptors show a differential subcellular localization in human SSR positive tumors. The use of SSR subtype selective antibodies to detect the subcellular distribution of SSR subtypes in individual tumor cells is an important step forward to understand more about the pathophysiological role of the different SSR subtypes in human tumors

Somatostatin receptor subtypes in human thymoma and inhibition of cell proliferation by octreotide in vitro

Somatostatin (SS) and SS receptor (SSR) subtypes, code-named sst1-5, are heterogeneously expressed in the normal human thymus. This suggests their involvement in controlling the immune and/or neuroendocrine functions in this organ. Moreover, recently a high in vivo uptake of [111In-DTPA-D-Phe1]octreotide has been reporte

Somatostatin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Somatostatin (somatotropin release inhibiting factor) is an abundant neuropeptide, which acts on five subtypes of somatostatin receptor (SST1-SST5; nomenclature as agreed by the NC-IUPHAR Subcommittee on Somatostatin Receptors [89]). Activation of these receptors produces a wide range of physiological effects throughout the body including the inhibition of secretion of many hormones. Endogenous ligands for these receptors are somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28). cortistatin-14 has also been suggested to be an endogenous ligand for somatostatin receptors [56]

Somatostatin receptors in GtoPdb v.2023.1

Somatostatin (somatotropin release inhibiting factor) is an abundant neuropeptide, which acts on five subtypes of somatostatin receptor (SST1-SST5; nomenclature as agreed by the NC-IUPHAR Subcommittee on Somatostatin Receptors [98]). Activation of these receptors produces a wide range of physiological effects throughout the body including the inhibition of secretion of many hormones. Endogenous ligands for these receptors are somatostatin-14 (SRIF-14) and somatostatin-28 (SRIF-28). cortistatin-14 has also been suggested to be an endogenous ligand for somatostatin receptors [61]

A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants

A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops

In silico design and biological evaluation of a dual specificity kinase inhibitor targeting cell cycle progression and angiogenesis

Methodology: We have utilized a rational in silico-based approach to demonstrate the design and study of a novel compound that acts as a dual inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2) and cyclin-dependent kinase 1 (CDK1). This compound acts by simultaneously inhibiting pro-Angiogenic signal transduction and cell cycle progression in primary endothelial cells. JK-31 displays potent in vitro activity against recombinant VEGFR2 and CDK1/cyclin B proteins comparable to previously characterized inhibitors. Dual inhibition of the vascular endothelial growth factor A (VEGF-A)-mediated signaling response and CDK1-mediated mitotic entry elicits anti-Angiogenic activity both in an endothelial-fibroblast co-culture model and a murine ex vivo model of angiogenesis