Destruction of Neurokinin-1 Receptor Expressing Cells in Vitro and in Vivo Using Substance P-saporin in Rats

Substance P (SP) acts on neurons through the neurokinin-1 (NK-1) receptor. Conjugation of SP to the ribosome inactivating protein, saporin (SAP), produces a cytotoxin selective for cells that express the NK-1 receptor. SP-SAP cytotoxicity was inhibited by pre-treating the toxin to reduce the disulfide bond connecting SP to SAP or by pre-incubation with anti-SP antiserum or by SP analog showing that SP-SAP acts through binding of the SP moiety to NK-1 receptors. Injection of SP-SAP into the striatum selectively destroyed NK-1 receptor expressing interneurons. These results show that SP-SAP will be useful for studying the function of NK-1 receptor expressing neurons.