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 neurokinin1 receptor agonist [Sar9, Met(O2)11] substance P and were antagonized by the neurokinin1 receptor antagonist SR140333. [Sar9, Met(O2)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 GTPgammaS within neurons implicating the involvement of a G-protein. The [Sar9, Met(O2)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 neurokinin1 receptors depolarize cholinergic interneurons in the rat striatum primarily through a phosphoinositide signalling pathway.