Targeting neurokinin-1 receptor-expressing neurons with [Sar(9),Met(O-2)(11)]substance P-saporin

Neurons expressing neurokinin-l 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 neuron s even at doses that produce non-specific damage. In the present study, we sought to determine if the more stable, NK-1 R-specific SP analog conjugate d to saporin, [Sar(9),Met(O-2)(11)]-SP (SSP-saporin), would selectively des troy cells expressing NK-1R, in vitro and in vivo. The results show that SS P-saporin is highly effective and selective, producing extensive ablation o f striatal NK-1R expressing interneurons at doses that do not cause loss of other striatal neurons suggesting advantages over SP-saporin as a selectiv e lesioning agent. SSP-saporin will be useful in larger species and for int raparenchymal injections. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.