Facilitation of cholinergic transmission by substance P methyl ester in the mouse hippocampal slice preparation.
Using sharp microelectrode recording from CA1 pyramidal neurons of the adult mouse hippocampal slice preparation, we studied the modulatory action of the selective neurokinin 1 (NK1) receptor agonist substance P methyl ester (SPME), a peptidase-resistant analogue of the peptide substance P (SP), on cholinergic responses. While SPME (0.1-1 microM) had only slight effects on membrane potential and input resistance of CA1 neurons, it largely and reversibly enhanced the membrane depolarization and oscillatory activity induced by the cholinergic agonist carbachol (CCh; 0.1-100 microM). This effect of SPME was prevented by the selective NK1 receptor antagonist SR 140333 (4 microM). In about half of the tested neurons the action of SPME was preserved in tetrodotoxin (TTX) solution, suggesting that it partly occurred at the level of pyramidal cells. Cholinergic slow excitatory postsynaptic potentials (sEPSPs) were reversibly enhanced by SPME which increased their amplitude and prolonged any associated bursting activity. This action was also blocked by SR 140333. The present results suggest that SPME largely enhances cholinergic activity in the mouse hippocampus, an effect which can help to explain, in this brain area, the recently reported facilitation of seizures by SP.
Kouznetsova
M
M
Biophysics Sector and INFM Unit, International School for Advanced Studies (SISSA), 34014 Trieste, Italy.
Nistri
A
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000109:Acetylcholine / Q000502:physiology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D018679:Cholinergic Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D011812:Quinuclidines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D018040:Receptors, Neurokinin-1 / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018679:Cholinergic Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010880:Piperidines; D011812:Quinuclidines; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; C085215:SR 140333; D013373:Substance P; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C033611:substance P, methyl ester-; C056639:2-amino-5-phosphopentanoic acid; D001285:Atropine; D002217:Carbachol; D014633:Valine; D000109:Acetylcholine; D001640:Bicuculline