Abstract:
:N- and C-terminal substance P (SP) fragments increase striatal dopamine outflow at nanomolar concentrations. This contrasts with their low affinity for NK1 receptors. To explore this discrepancy, we investigated the interaction of SP and SP fragments with NK1 sites in fresh striatal slices, the same model used in the functional studies on dopamine outflow. [3H]SP bound specifically to one site (Kd = 6.6 +/- 0.9 nM; Bmax = 12.6 +/- 0.7 fmol/mg protein). [3H]SP binding was displaced by SP (IC50 = 11.8 nM), but not by SP(1-7) or SP(5-11), up to 10 microM. In contrast, 10 nM SP(1-7) or SP(5-11) induced significant internalization of the NK1 receptor, similar to that induced by SP. We suggest that SP fragments have high affinity for an NK1 receptor conformer which is different from that labelled by [3H]SP.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Michael-Titus AT,Blackburn D,Connolly Y,Priestley JV,Whelpton Rdoi
10.1097/00001756-199907130-00038subject
Has Abstractpub_date
1999-07-13 00:00:00pages
2209-13issue
10eissn
0959-4965issn
1473-558Xjournal_volume
10pub_type
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