N- and C-terminal substance P fragments: differential effects on striatal [H-3]substance P binding and NK1 receptor internalization

N- and C-terminal substance P (SP) fragments increase striatal dopamine out flow at nanomolar concentrations. This contrasts with their low affinity fo r NK1 receptors. To explore this discrepancy, we investigated the interacti on of SP and SP fragments with NK1 sites in fresh striatal slices, the same model used in the functional studies on dopamine outflow. [H-3]SP bound sp ecifically to one site (K-d = 6.6 +/- 0.9 nM; B-max = 12.6 +/- 0.7 fmol/mg protein). [H-3]SP binding was displaced by SP (IC50 = 11.8 nM), but not by SP(1-7) or SP(5-11), up to 10 mu M. In contrast, 10 nM SP(1-7) or SP(5-11) induced significant internalization of the NK1 receptor, similar to that in duced by SP. We suggest that SP fragments have high affinity for an NK1 rec eptor conformer which is different from that labelled by [H-3]SP. NeuroRepo rt 10:2209-2213 (C) 1999 Lippincott Williams & Wilkins.