Analog of Somatostatin Vapreotide Exhibits Biological Effects in vitro via Interaction with Neurokinin-1 Receptor

Objectives: Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P (SP)-preferring receptor. The ability of vapreotide to interfere with other biological effects of SP has yet to be investigated. Methods: We studied the ability of vapreotide to antagonize NK1R in three different cell types: immortalized U373MG human astrocytoma cells, human monocyte-derived macrophages (MDM) and a human embryonic kidney cell line, HEK293. Both U373MG and MDM express endogenous NK1R while HEK293 cells, which normally do not express NK1R, are stably transformed to express human NK1R (HEK293-NK1R). Results: Vapreotide attenuates SP-triggered intracellular calcium increases and nuclear factor-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced interleukin-8 and monocyte chemotactic protein-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in Received: January 30, 2013 Accepted after revision: March 4, 2013 Published online: July 5, 2013 Steven D. Douglas, MD Division of Allergy and Immunology The Children’s Hospital of Philadelphia 34th Street and Civic Center Blvd., Philadelphia, PA 19104 (USA) E-Mail DOUGLAS @ email.chop.edu © 2013 S. Karger AG, Basel 1021–7401/13/0205–0247$38.00/0