PMID- 2906296 OWN - NLM STAT- MEDLINE DCOM- 19890329 LR - 20190721 IS - 0014-4819 (Print) IS - 0014-4819 (Linking) VI - 73 IP - 3 DP - 1988 TI - Structural requirements for activation of excitatory amino acid receptors in the rat spinal cord in vitro. PG - 541-5 AB - The conformational requirements for activation of N-methyl-D-aspartate (NMDA) and quisqualate (QUIS) excitatory amino acid receptors on rat spinal neurones in vitro have been examined using a number of conformationally restricted compounds related to L-glutamate (L-GLU). The excitants were assigned to a receptor type on the basis of their susceptibility to blockade by D (-)-2-amino-5-phosphonvalerate (DAPV) and kynurenate (KYNA). When iontophoretically applied to unidentified neurones in the dorsal horn of spinal cord slices maintained in vitro, three of the isomers of 1-amino-1,3-cyclopentane dicarboxylate (ACPD) evoked excitations which were DAPV-sensitive and therefore were probably elicited via NMDA receptors. The fourth isomer (D-trans-(1R,3S)-ACPD) resembled quinolinate (QUIN) in its actions, and differed from both NMDA and QUIS. Several pyridine derivatives in addition to QUIN were tested, and both the 2,5- and 2,6-pyridine dicarboxylates evoked excitations which, like those produced by QUIS and L-GLU, were largely unaffected by both DAPV and KYNA and thus appeared due to activation of the QUIS receptor. 2,4-Pyridine dicarboxylate acted as a weak and unselective antagonist of amino acid-induced excitations. The results support an earlier conclusion that compounds reacting with the NMDA receptor do so in an extended configuration whereas the QUIS receptor has a more folded template. The possibility that QUIN reacts with a receptor different from those activated by other amino acids is considered. FAU - Magnuson, D S AU - Magnuson DS AD - Department of Physiology, University of British Columbia, Vancouver, Canada. FAU - Curry, K AU - Curry K FAU - Peet, M J AU - Peet MJ FAU - McLennan, H AU - McLennan H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Exp Brain Res JT - Experimental brain research JID - 0043312 RN - 0 (Receptors, AMPA) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Receptors, Neurotransmitter) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - H030S2S85J (Kynurenic Acid) RN - HG18B9YRS7 (Valine) SB - IM MH - 2-Amino-5-phosphonovalerate MH - Action Potentials/drug effects MH - Animals MH - In Vitro Techniques MH - Kynurenic Acid/pharmacology MH - Male MH - Protein Conformation MH - Rats MH - Rats, Inbred Strains MH - Receptors, AMPA MH - Receptors, N-Methyl-D-Aspartate MH - Receptors, Neurotransmitter/drug effects/*metabolism MH - Spinal Cord/drug effects/*metabolism MH - Valine/analogs & derivatives/pharmacology EDAT- 1988/01/01 00:00 MHDA- 1988/01/01 00:01 CRDT- 1988/01/01 00:00 PHST- 1988/01/01 00:00 [pubmed] PHST- 1988/01/01 00:01 [medline] PHST- 1988/01/01 00:00 [entrez] AID - 10.1007/BF00406612 [doi] PST - ppublish SO - Exp Brain Res. 1988;73(3):541-5. doi: 10.1007/BF00406612.