title: Glutamate receptors of the N-methyl-D-aspartate subtype in the myenteric plexus of the guinea pig ileum.
abstract: The excitatory amino acids L-glutamate and N-methyl-D-aspartate (NMDA) produced contractions of the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum over the concentration range of 3 X 10(-6) to 10(-3) M. The contractile response to L-glutamate and NMDA, but not carbamyl choline, was blocked noncompetitively by 0.6 mM Mg++. In the absence of Mg++, concentration-dependent increases in contractile force also were produced by, in order of potency, L-aspartate, L-homocysteate and D-glutamate, but not by quisqualate, kainate or quinolinate. L-Glutamate was competitively antagonized by the selective NMDA receptor antagonists D-2-amino-5-phosphonovalerate and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (3 X 10(-6)-3 X 10(-5) M), as well as by the nonselective excitatory amino acid antagonist gamma-D-glutamylglycine (3 X 10(-4) M). Glutamic acid diethyl ester (3 X 10(-4) M) noncompetitively antagonized L-glutamate. L-Glutamate was not blocked by gamma-D-glutamylaminomethyl sulphonate (3 X 10(-4) M), an antagonist which preferentially antagonizes kainate and quisqualate. In addition, the phencyclidine-like drugs etoxadrol (10(-7)-10(-5) M), dextromethorphan (10(-6)-10(-5) M) and 5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine (10(-9)-10(-7) M) noncompetitively antagonized L-glutamate. The (+) isomer of 5-methyl-10, 11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine was approximately 10-fold more potent than the (-) isomer in antagonizing L-glutamate. The present results demonstrate that receptors for the excitatory amino acid L-glutamate are present in the guinea pig myenteric plexus and are of the NMDA subtype.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana.
authors.forename: H E
authors.initials: HE
authors.lastname: Shannon
authors.forename: B D
authors.initials: BD
authors.lastname: Sawyer
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006168:Guinea Pigs; D007082:Ileum / Q000032:analysis* / Q000187:drug effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000032:analysis*; D016202:N-Methylaspartate; D010879:Piperazines / Q000494:pharmacology; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000032:analysis*
chemical_list: D003986:Dibenzocycloheptenes; D005971:Glutamates; D010879:Piperazines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium