MK-801 blocks nicotinic depolarizations of guinea pig myenteric neurons.
Intracellular recordings were made from guinea-pig myenteric neurons. Acetylcholine (ACh), applied by iontophoresis, produced a depolarization that was blocked by hexamethonium (EC50 3.2 microM) but not by scopolamine (1 microM). MK-801 (0.3-30 microM), a non-competitive antagonist at N-methyl-D-aspartate receptors, also blocked the nicotinic depolarization (EC50 = 4.5 microM). Voltage clamp measurements of membrane current showed that MK-801 (1 microM) and hexamethonium (1 microM) both produced a greater inhibition of ACh-induced inward currents at -100 mV than at -40 mV. MK-801 (10 microM) did not change the depolarization evoked by 5-HT (acting at 5-HT3 receptors) in the same neurons in which it reduced the nicotinic response by more than 70%. It is concluded that MK-801 can act as a non-competitive antagonist of nicotinic responses in myenteric neurons.
Galligan
J J
JJ
Vollum Institute, Oregon Health Sciences University, Portland 97201.
North
R A
RA
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007082:Ileum / Q000294:innervation; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic / Q000502:physiology*
D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D006584:Hexamethonium Compounds; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D016291:Dizocilpine Maleate; D000109:Acetylcholine