Receptor somatostatin

Indium-111. Kits for labeling using other radionucHdes include two indium-111 compounds. Indium-111 pentetreotide is used for the scintigraphic localization of primary and metastatic neuroendocrine tumors bearing somatostatin receptors. For octreotide DTP A, the active agent is suppHed in a lyopbilized kit with gentisic acid, citrate buffer, and inositol. 

Somatostatin Receptor Scintigraphy and Receptor-Targeted Radiotherapy... 

Hoyer D, Epelbaum J, Feniuk W, Humphrey PPA, Meyerhof W, O caroll AM, Patel Y, Reisine T, Reubi JC, Schindler M, Schonbmnn A, Taylor JOB, Vezzani A (2000) Somatostatin receptors. In Watson SP, Girdlestone D, ed. The IUPHAR compendium of Receptor Characterization and Classification, 2nd edn., pp. 354—364. London IUPHAR Media... 

Sun L., Fuselier J.A., Murphy W.A., Coy D.H. Antisense peptide nucleic acids conjugated to somatostatin analogs and targeted at the n-myc oncogene display enhanced cytotoxity to human neuroblastoma 1M.R.32 cells expressing somatostatin receptors. Peptides 2002 23 1557-1565. 

The GABAb receptors were the first G-protein-coupled receptors to be observed to form functional heterodimers (Bowery and Enna 2000) where two G-protein molecules come together to act as a dimer to enhance their combined response. A similar effect has recently also been described for dopamine and somatostatin receptors (Rocheville et al. 2000) and it is likely that this may occur with other G-protein-coupled receptors. The significance of this in terms of the pharmacology of the receptors is unclear, or indeed whether dimerisation affects mechanisms such as desensitisation. 

Fig. 10. N4 ligand systems for conjugation 99mTc to biomolecules R = in vivo targeting biomolecules (e.g., biotin [100, 101], somatostatin receptor-avid peptide [103,104])...

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 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. 

The k receptor was cloned by a completely different approach. Yasuda et al. [9] employed probes against conserved regions of somatostatin receptors to screen a mouse brain cDNA library. Mouse k and 3 receptor cDNAs were isolated using this procedure that established that opiate and somatostatin receptors have high amino acid sequence similarity, consistent with their ability to bind some common ligands, such as Sandostatin. 

The desensitization of the fi receptor was heterologous. In oocytes cotransfected with ft and serotonin receptors, chronic morphine treatment abolished morphine and serotonin potentiation of the K+ current [63]. Similarly, in AtT-20 cells transfected with the cloned fi receptor, chronic DAMGO treatment abolished the ability of opiates and somatostatin, acting via endogenous somatostatin receptors in these cells, to stimulate K+ conductance [65]. 

Law SF, Yasuda K, Bell GI, Reisine T. Gia3 and Goa selectively associate with the cloned somatostatin receptor subtype... 

Kong H, Raynor K, Yasuda K, Bell GI, Reisine T. Mutation of an aspartate at residue 89 in somatostatin receptor sub-type 2 prevents Na regulation of agonist binding but does not alter receptor/G protein association. Mol Pharmacol 1993 44 380-384. 

Liapakis G, Fitzpatrick D, Hoeger C, Rivier ], Vandlen R, Reisine T. Identification of ligand binding determinants in the somatostatin receptor subtypes 1 and 2. J Biol Chern 1996 271 20331-20339. 

Patel, R. C., Lange, D. C. and Patel, Y. C. (2002). Photobleaching fluorescence resonance energy transfer reveals ligand-induced oligomer formation of human somatostatin receptor subtypes. Methods 27, 340-8. 

Patel, R. C Kumar, U Lamb, D. C., et al. (2002) Ligand binding to somatostatin receptors induces receptors-specific oligomer formation in live cells. Proc. Natl. Acad. Sci. USA 99, 3294-3299. 

Pfeiffer, M., Koch, T., Schroder, H., et al. (2001) Homo- and heterodimerization of somatostatin receptor subtypes. Inactivation of sst(3) receptor function by heterodimerization with sst(2A). J. Biol. Client. 276,14027-14036. 

Roth, A., Kreienkamp, H. J., Meyerhof, W., and Richter, D. (1997) Phosphorylation of four amino acid residues in the carboxyl terminus of the rat somatostatin receptor subtype 3 is crucial for its desensitization and intemahzation. J. Biol. Chem. 272, 23769-23774. 

Rohree, S.P., Biezin, E.T., Mosley, R.T., Berk, S.C., Hutchins, S.M., Shen, D.M., Xiong, Y., Hayes, E.C. Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science 1998, 282, 737-740. 

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