Targeting neurokinin-1 receptor-expressing neurons with [Sar9,Met(O2)11 substance P-saporin.
Neurons expressing neurokinin-1 receptors (NK-1R) are selectively destroyed by substance P (SP) coupled to the ribosome inactivating protein, saporin. SP-saporin produces incomplete lesions of striatal NK-1R-expressing neurons even at doses that produce non-specific damage. In the present study, we sought to determine if the more stable, NK-1R-specific SP analog conjugated to saporin, [Sar9,Met(O2)11]-SP (SSP-saporin), would selectively destroy cells expressing NK-1R, in vitro and in vivo. The results show that SSP-saporin is highly effective and selective, producing extensive ablation of striatal NK-1R expressing interneurons at doses that do not cause loss of other striatal neurons suggesting advantages over SP-saporin as a selective lesioning agent. SSP-saporin will be useful in larger species and for intraparenchymal injections.
Wiley
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RG
Neurology Service (127), VAMC, Nashville, TN 37212-2637, USA. ronald.g.wiley@vanderbilt.edu
Lappi
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DA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D000922:Immunotoxins; D008297:Male; D009699:N-Glycosyl Hydrolases; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010940:Plant Proteins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D013373:Substance P / Q000031:analogs & derivatives* / Q000633:toxicity
D000972:Antineoplastic Agents, Phytogenic; D000922:Immunotoxins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D009699:N-Glycosyl Hydrolases; D000076985:Saporins