Characterization of the mechanism of action of tachykinins in rat striatal cholinergic interneurons

The mechanism by which substance P depolarizes cholinergic interneurons in the rat striatum was studied using whole-cell recording techniques. In all cases the effects of substance P were mimicked by the neurokinin(1) receptor agonist [Sar(9), Met(O-2)(11)] substance P and were antagonized by the neurokinin(1) receptor antagonist SR 140333. [Sarg(9) Met(O-2)(11)] substance P was found to depolarize cholinergic interneurons by the induction of a calcium-activated inward current at - 60 mV. This inward current was irreversibly potentiated by photolysis of caged GTP gamma S within neurons implicating the involvement of a G-protein. The [Sarg(9) Met(O-2)(11)] substance P-induced inward current was inhibited by the phospholipase C inhibitor U-73122, and by the inclusion of the inositol-1,4.5-triphosphate receptor antagonist heparin in the electrode solution. These findings suggest that neurokinin(1) receptors depolarize cholinergic interneurons in the rat striatum primarily through a phosphoinositide signalling pathway. (C) 1998 IBRO. Published by Elsevier Science Ltd.