Pharmacological Characterization of a Recombinant, Fluorescent Somatostatin Receptor Agonist

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• 作者：Varun K. A. Sreenivasan ; Oleg A. Stremovskiy ; Timothy A. Kelf ; Marika Heblinski ; Ann K. Goodchild ; Mark Connor ; Sergey M. Deyev ; Andrei V. Zvyagin
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：September 21, 2011
• 年：2011
• 卷：22
• 期：9
• 页码：1768-1775
• 全文大小：890K
• 年卷期：v.22,no.9(September 21, 2011)
• ISSN：1520-4812

文摘

Somatostatin (SST) is a peptide neurotransmitter/hormone found in several mammalian tissue types. Apart from its natural importance, labeled SST/analogues are utilized in clinical applications such as targeting/diagnosis of neuroendocrine tumors. We report on the development and characterization of a novel, recombinant, fluorescent somatostatin analogue that has potential to elucidate somatostatin-activated cell signaling. SST was genetically fused with a monomeric-red fluorescent protein (mRFP) as the fluorescent label. The attachment of SST to mRFP had no detectable effect on its fluorescent properties. This analogue鈥檚 potency to activate the endogenous and transfected somatostatin receptors was characterized using assays of membrane potential and Ca²⁺ mobilization and immunocytochemistry. SST-mRFP was found to be an effective somatostatin receptor agonist, able to trigger the membrane hyperpolarization, mobilization of the intracellular Ca²⁺ and receptor鈥搇igand internalization in cells expressing somatostatin receptors. This complex represents a novel optical reporter due to its red emission spectral band suitable for in vivo imaging and tracking of the somatostatin receptor signaling pathways, affording higher resolution and sensitivity than those of the state-of-the-art radiolabeling bioassays.