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.
Parke Davis Neuroscience Research Centre, and MRC Cambridge Centre For Brain Repair, Cambridge University Forvie Site, UK.
M I
MI
Bell
P J
PJ
Richardson
K
K
Lee
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002614:Chelating Agents; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology*; D003979:Diazonium Compounds; D004558:Electric Stimulation; D004963:Estrenes / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D007395:Interneurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010642:Phenoxyacetates; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010777:Photochemistry; D010880:Piperidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D015320:Tachykinins / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D002614:Chelating Agents; D003979:Diazonium Compounds; D004963:Estrenes; D018691:Excitatory Amino Acid Antagonists; D010642:Phenoxyacetates; D010726:Phosphodiesterase Inhibitors; D010880:Piperidines; D011760:Pyrrolidinones; D011810:Quinoxalines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C062618:substance P, Sar(9)-Met(O2)(11)-; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C063685:diazo-2; C085215:SR 140333; D013373:Substance P; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D000109:Acetylcholine