Substance P-(1–7) and substance P-(5–11) locally modulate dopamine release in rat striatum

Abstract

The effects of substance P, substance P-(1–7) and substance P-(5–11) on endogenous dopamine outflow in rat striatal slices were investigated. The dose-response curves (0.01 nM to 10 μM) were bell-shaped, with significant increases at 0.1 and 1 nM but with no effect at higher concentrations. The tachykinin NK 1 receptor agonist, [Sar 9,Met(O 2) 11]substance P, significantly increased dopamine outflow at 10 and 100 nM. The effects of substance P or substance P-(5–11) and 25 mM KCl were additive. A negative interaction was observed with substance P-(1–7) and K +. The increase in dopamine outflow elicited by 1 nM substance P and substance P-(5–11) was reversed by the tachykinin NK 1 receptor antagonist WIN 51,708 (17β-hydroxy-17α-ethynyl-5α-androstano[3,2-b]pyrimido[1,2-a]benzimidazole) (25 and 250 nM), whereas only partial reversal was observed for the effect of substance P-(1–7). These results show that substance P fragments locally modulate striatal dopamine outflow and the mechanisms underlying this modulation may differ between N-and C-terminal fragments.