Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to resolve multiple fluorophores by their lifetimes in discrete tissue domains, the labeling intensity must be sufficiently strong and the intensity-difference between the labels must not be too large, the rate of fading should be similar for all fluorophores, and the lifetimes of the fluorophores should be sufficiently discrete. We could readily distinguish Cyanine-3.18 (Cy-3), Lissamine Rhodamine (LRSC), and Texas Red when they were not colocalized in tissue profiles. Colocalization of Cy-3 and LRSC, as well as Cy3 and Texas Red, could also be distinguished, while the combination of LRSC and Texas Red was more difficult. We have used fluorescence lifetime recordings in confocal microscopy to detect different neuropeptides in neurons. We demonstrate that somatostatin and galanin are colocalized in axon profiles of the spinal cord dorsal horn.
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PMID:Fluorescence lifetime measurements in confocal microscopy of neurons labeled with multiple fluorophores. 909 41

Somatostatin receptor (SSTR) endocytosis influences cellular responsiveness to agonist stimulation and somatostatin receptor scintigraphy, a common diagnostic imaging technique. Recently, we have shown that SSTR1 is differentially regulated in the endocytic and recycling pathway of pancreatic cells after agonist stimulation. Additionally, SSTR1 accumulates and releases internalized somatostatin-14 (SST-14) as an intact and biologically active ligand. We also demonstrated that SSTR2A was sequestered into early endosomes, whereas internalized SST-14 was degraded by endosomal peptidases and not routed into lysosomal degradation. Here, we examined the fate of peptide agonists in rat insulinoma cells expressing SSTR3 by biochemical methods and confocal laser scanning microscopy. We found that [(125)I]Tyr11-SST-14 rapidly accumulated in intracellular vesicles, where it was degraded in an ammonium chloride-sensitive manner. In contrast, [(125)I]Tyr1-octreotide accumulated and was released as an intact peptide. Rhodamine-B-labeled SST-14, however, was rapidly internalized into endosome-like vesicles, and fluorescence signals colocalized with the lysosomal marker protein cathepsinD. Our data show that SST-14 was cointernalized with SSTR3, was uncoupled from the receptor, and was sorted into an endocytic degradation pathway, whereas octreotide was recycled as an intact peptide. Chronic stimulation of SSTR3 also induced time-dependent downregulation of the receptor. Thus, the intracellular processing of internalized SST-14 and the regulation of SSTR3 markedly differ from the events mediated by the other SSTR subtypes.
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PMID:Intracellular degradation of somatostatin-14 following somatostatin-receptor3-mediated endocytosis in rat insulinoma cells. 1870 62

Over-expression of the somatostatin-2 (SST2) receptor on plasma membranes of neuroendocrine cancer cells renders it attractive for use in targeting both imaging and therapeutic agents to neuroendocrine tumors. Peptide analogs of somatostatin have dominated this approach to date, however, many peptide analogs are either unstable in vivo or exhibit unwanted non-specific uptake in the liver and kidneys. The purpose of this Letter is to describe the preparation and evaluation of a non-peptide SST2 agonist for use in targeting drugs to neuroendocrine cancers. A non-peptide ligand for the SST2 receptor was identified from the literature as a candidate for development of targeted pharmaceuticals for neuroendocrine tumors, based on its SST2 binding affinity and selectivity for SST2 over other somatostatin receptors. It also offered a multiplicity of possible conjugation sites. Rhodamine conjugates in two positions were used for optical imaging and two compounds were internalized in an SST2 receptor transduced cell line (C6-SST2) via SST2 receptor-mediated endocytosis. Radionuclide conjugates were prepared for in vivo imaging and biodistribution studies in mice. The in vitro binding affinity of (99m)Tc conjugates ranged from a Kd of 37-494. Of these, one (99m)Tc conjugate was selected and dosed by IV injection into mice bearing C6-SST2 tumor xenografts. The highest uptake was into tumor, intestine and skin four hours after IV injection. Competition studies with octreotide, a synthetic peptide and SST2 agonist, confirmed that uptake was SST2 receptor mediated. While relatively high uptake in intestine, liver, kidneys and skin discouraged further development of the conjugate for delivery of chemotherapeutic agents, the conjugate may still be worthy of further development for neuroendocrine tumor imaging.
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PMID:Synthesis and evaluation of a ligand targeting the somatostatin-2 receptor for drug delivery to neuroendocrine cancers. 2579 53