Somatostatin receptor-specific peptide

The synthesis and characterization of a somatostatin receptor-specific peptide H2N-(DPhe)-cyclo[Cys-Phe-(D-Trp)-Lys-Thr-Cys]-Thr-OH, labeled with an indo-dicarbo- and an indotricarbocyanine dye at the V-terminal amino group were described in [34], The ability of these fluorescent contrast agents to target the somatostatin receptor was demonstrated by flow cytometry in vitro, wherein the indotricarbocyanine conjugate led to elevated cell-associated fluorescence on somatostatin receptor-expressing tumor cells. The intracellular localization was visualized using NIR fluorescence microscopy. 

Cortistatin is synthesized as a precursor of 116 amino acids that gives rise to a C-terminal mature peptide, cortistatin-14 (CST-14), that shares 11 of its 14 residues with the neuropeptide somatostatin. However, the similarities between cortistatin and somatostatin are restricted to the mature peptides, which are the products of different genes. CST-14 binds to all five somatostatin receptors in vitro, although several authors suggest that CST-14 exerts its actions in vivo by binding to its own specific receptor (Spier de Lecea, 2000). 

The peptide hormone somatostatin inhibits secretion from a wide variety of both endocrine and exocrine cells. It functions as a neurotransmitter and plays an important role in the regulation of cell proliferation and differentiation. Somatostatin exerts its effects through binding to specific surface membrane receptors. Somatostatin receptors are membrane glycoproteins with five different subtypes distributed in a variety of tissues throughout the body. 

Determination of specific binding of the labelled peptides to biological materials was carried out with D341 Med human medulloblastoma cells derived from a tumour biopsy from a patient with a cerebellar medulloblastoma, which expresses high levels of somatostatin receptors. The cells were maintained as a continuous cell line in 10% foetal calf serum and zinc option media in a humidified atmosphere (37°C, 5% CO,). 

NET cells are characterized by their ability to take up and concentrate amine precursors such as dihydroxy-phenylalanine (DOPA) and hydroxytryptophane (HTP) and to produce amines and peptides, for which reason they were also classified as amine precursor uptake and decarboxylation (APUD) cells. They may also express different peptide hormone receptors (like somatostatin receptors) or transporters at their cell membrane. These uptake mechanisms and the presence of peptide receptors and transporters constitute the basis for the use of specific radiolabeled ligands for imaging of neuroendocrine tumors. 

For all other indications in NET, Ga or F-labeled somatostatin analogs will mainly enhance diagnostic workup and wiU probably become the tracers of first choice in this tumor entity. The development of somatostatin analogs with broader range of receptor affinity wiU potentially further improve this approach. Furthermore, this method and the ease of quantification will contribute to a more precise evaluation of patients eligible for specific therapy Hke biotherapy with somatostatin analogs or peptide receptor radionucHde therapy. 

Neuropeptide Y [NPY] is a 36-amino acid peptide. The function of NPY, one of the most abundant peptide transmitters of the mammalian brain, remains unclear because of a lack of specific receptor antagonists. NPY meets many of the criteria of a neurotransmitter itself. NPY is costored and interacts with several monoaminergic neurons within the CNS [Lundberg et al. 1982], for example, noradrenergic afferents from the nucleus solitary tract to the amygdala. Both somatostatin and NPY colocalize at GABA interneurons within the amygdala, neocortex, and striatum. NPY also selectively modulates N-methyl-D-aspartate-induced hippocampal activation (pyramidal neurons] via oreceptors [Debonnel et al. 1994]. 

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