Effects of nicotinic agonists and antagonists on N-methyl-D-aspartate-induced 3H-norepinephrine release and 3H-(1-[1-(2-thienyl)cyclohexyl]-piperidine) binding in rat hippocampus.
The nicotinic agonists dimethylphenylpiperazinium iodide (DMPP) and carbachol (CARB) as well as (-)nicotine [-)NIC) were tested alone and in combination with N-methyl-D-aspartate (NMDA) for their abilities to enhance the efflux of 3H-norepinephrine (NE) from slices of rat hippocampus. CARB and (-)NIC produced small, transient increases in NE efflux, while DMPP produced larger, longlasting increases. Inasmuch as the nicotinic antagonists mecamylamine (MECA) and hexamethonium (C6) did not consistently inhibit the increases in NE efflux produced by these agonists, the role of a nicotinic receptor in mediating these responses is uncertain. CARB and DMPP enhanced the ability of NMDA to stimulate NE release, while (-)NIC did not. MECA, but not C6, was found to selectively antagonize NMDA-stimulated NE release that did not appear to involve a nicotinic receptor. Binding studies indicated that MECA and the related nicotinic antagonist pempidine produced an inhibition of NMDA-stimulated NE release by an action at the PCP receptor that is known to be linked to the NMDA receptor-ionophore complex. These data suggest that the actions of these ganglionic blocking agents on excitatory responses in the hippocampus involve inhibition of excitatory amino acid as well as nicotinic receptors.
Snell
L D
LD
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Johnson
K M
KM
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008464:Mecamylamine / Q000494:pharmacology; D016202:N-Methylaspartate; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
D005731:Ganglionic Stimulants; D006584:Hexamethonium Compounds; D011978:Receptors, Nicotinic; D001224:Aspartic Acid; D018738:Hexamethonium; D004246:Dimethylphenylpiperazinium Iodide; D016202:N-Methylaspartate; D008464:Mecamylamine; D009538:Nicotine; D002217:Carbachol; D009638:Norepinephrine