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Neurosci Lett. 1999 Dec 17;277(1):1-4.

Targeting neurokinin-1 receptor-expressing neurons with [Sar9,Met(O2)11 substance P-saporin.

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  • 1Neurology Service (127), VAMC, Nashville, TN 37212-2637, USA.


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.

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