Neurokinin Receptors Differentially Mediate Endogenous Acetylcholine Release Evoked by Tachykinins in the Neostriatum

The regulation of neostriatal cholinergic function by tachy-kinins (TKs) has been studied by measuring endogenous ACh released from rat neostriatal slices. Septide (SEP; a highly selective substance P analog), neurokinin A (NKA), and neurokinin B (NKB) elicited endogenous ACh release in a concentration-dependent manner. The rank order in po-tency was the following: NKB (EC,, = 0.5 nM)> NKA (EC, = 7 nu)> SEP (EC,, = 12 nM). Spantide (SPA) was less effective (39 % inhibition) than [D-Args, D-Trp7.9, KMethyl-Phea]-substance P fragment 6-11 (53 % inhibition) at antag-onizing ACh release evoked by SEP and NKA. Smaller doses of the antagonists inhibited the effects of SEP compared to NKA, and the effects of NKB could only be antagonized by SPA. These findings suggest the involvement of the three neurokinin (NK) receptors in ACh release evoked by TK