Tachykinins increase [H-3]acetylcholine release in mouse striatum through multiple receptor subtypes

Tachykinins have been suggested to play a significant role in the mammalian striatum, at least in part by the control of acetylcholine release from ch olinergic interneurons. In the present study, we have examined the ability of known tachykinin agonists and antagonists to modulate the activity of th ese interneurons in mouse striatal slices. Using whole-cell patch-clamp rec ordings, the selective neurokinin-1, neurokinin-2 and neurokinin-3 receptor agonists [sar(9),Met(O-2)(11)] substance P, [beta-ala(8)]neurokinin A(4-10 ) and senktide each produced a dose-dependent depolarization of visually id entified cholinergic interneurons that was retained under conditions design ed to interrupt synaptic transmission. The nature of these neurons and the expression of multiple tachykinin receptors was confirmed using single-cell reverse transcriptase-polymerase chain reaction analysis. Using in vitro s uperfusion techniques, the selective neurokinin-l, neurokinin-2 and neuroki nin-3 receptor agonists [sar(9),Met(O-2)(11)]substance P, [beta-ala(8)]neur okinin A(4-10) and senktide, respectively, each produced a dose-dependent i ncrease in acetylcholine release, the selectivity of which was confirmed us ing the neurokinin-l, neurokinin-2 and neurokinin-3 receptor antagonists SR 140333, GR94800 and SR142801 (100 nM). U73122 (10 mu M), a phospholipase C inhibitor, blocked [sar(9),Met(O-2)(11)]substance P- and senktide-induced a cetylcholine release, but had no effect on [beta-ala(8)]neurokinin A(4-10)- induced release. The protein kinase C inhibitors chelerythrine and Ro-31-82 20 (both 1 mu M) significantly inhibited responses induced by all three ago nists. These findings indicate that tachykinins modulate the activity of mouse str iatal cholinergic interneurons. Furthermore, neurokinin-2 receptors are sho wn to perform a role in mouse that has not been identified previously in ot her species. (C) 1999 IBRO. Published by Elsevier Science Ltd.