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)