RT Journal Article
SR Electronic
T1 N-methyl-D-aspartate receptor-mediated contractions of the guinea pig ileum longitudinal muscle/myenteric plexus preparation: modulation by phencyclidine and glycine receptors.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 754
OP 766
VO 257
IS 2
A1 Campbell, B G
A1 Couceyro, P
A1 Keana, J F
A1 Weber, E
YR 1991
UL http://jpet.aspetjournals.org/content/257/2/754.abstract
AB Glutamate evoked contractions of the longitudinal muscle/myenteric plexus (LMMP) preparation by an action at N-methyl-D-aspartate (NMDA) receptors. Other agonists at the NMDA recognition site, but not quisquilate or kainate, also contracted the LMMP, and glutamate-evoked contractions were competitively inhibited by selective NMDA receptor antagonists. Glutamate-evoked contractions were noncompetitively inhibited by MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine moleate], phencyclidine (PCP) and other compounds that bind to the PCP receptor, which is a binding site on the NMDA channel complex. Their potencies for this effect were highly correlated with their affinities for the PCP receptor. Glycine significantly shifted the glutamate concentration-response curve to the left. Glycine site antagonists caused a glycine-sensitive, noncompetitive inhibition of glutamate-evoked contractions, and their potencies for this effect were highly correlated with their affinities for the glycine binding site of the NMDA channel complex. Mg++ and Zn++ also noncompetitively inhibited glutamate-evoked contractions. The modulatory effects of glycine, Mg++, Zn++ and PCP receptor ligands were specific to glutamate-evoked contractions. MK-801 was highly selective for inhibition of glutamate-evoked contractions; MK-801 also inhibited nicotinic responses at a 500-fold lower potency. Two novel compounds are described that bind to the PCP receptor with high affinity and selectively inhibit glutamate-evoked contractions in the LMMP.