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.
Wiley
R G
RG
Neurology Service, VAMC, Nashville, TN 37212-2637, USA. wileyrg@ctrvax.vanderbilt.edu
Lappi
D A
DA
D000818:Animals; D015415:Biomarkers; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000032:analysis; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D007106:Immune Sera; D007150:Immunohistochemistry; D000922:Immunotoxins; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009699:N-Glycosyl Hydrolases; D010320:Parvalbumins / Q000032:analysis; D010940:Plant Proteins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013373:Substance P / Q000493:pharmacokinetics / Q000633:toxicity*; D014162:Transfection
D015415:Biomarkers; D007106:Immune Sera; D000922:Immunotoxins; D010320:Parvalbumins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D011994:Recombinant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D013373:Substance P; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins