Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion.
Using intracellular recording techniques, we examined the effects of tachykinin receptor agonists and antagonists on electrophysiologically identified tonic neurons of the isolated guinea pig coeliac ganglion. In most of the tonic neurons, substance P (SP), neurokinin A (NKA) and/or senktide induced a depolarization. The effects of SP and NKA were blocked by the NK1-selective antagonist, GR71251 (5 microM), but not by the NK2-selective antagonist, L659,877 (10 microM), whereas the effect of senktide was not affected by these antagonists. The NK1-selective agonists, [Sar9,Met(O)2(11)]SP and SP methyl ester, and the NK3-selective agonist, [MePhe7]neurokinin B, also evoked depolarizations in tonic neurons. By contrast, the NK2-selective agonists, [Nle10]NKA4-10, [beta-Ala8]NKA4-10 and GR64349, at 1 microM each, did not evoke any significant depolarizing response. Repetitive electrical stimulation of the mesenteric nerves induced slow excitatory postsynaptic potentials (EPSPs) in the majority of tonic neurons, which were depressed by GR71251 (5 microM). These results suggest that NK1 and NK3 receptors but not NK2 receptors are involved in the tachykinin-induced depolarization of tonic neurons, and that the NKA-induced response is due to the activation of NK1 receptors. This study also suggests the involvement of NK1 receptors in the slow EPSPs in tonic neurons.
Zhao
F Y
FY
Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Saito
K
K
Konishi
S
S
Guo
J Z
JZ
Murakoshi
T
T
Yoshioka
K
K
Otsuka
M
M
D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D015320:Tachykinins; C054724:senktide; C076254:GR 71251; D013373:Substance P; D015288:Neurokinin A