title: Quantitative studies of N-methyl-D-aspartate, 2-amino-5-phosphonovalerate and cis-2,3-piperidine dicarboxylate interactions on the neonatal rat spinal cord in vitro.
abstract: The interactions between N-methyl-D-aspartate (NMDA), (+/-)2-amino-5-phosphonovalerate (2AP5) and (+/-)cis-2.3-piperidine dicarboxylate (cis-PDA) were examined quantitatively in the neonatal rat spinal cord in vitro. NMDA and cis-PDA evoked concentration-dependent motoneuronal depolarizations. The maximal cis-PDA-evoked response was approximately 60% of that evoked by NMDA. When applied in combination with fixed concentrations of cis-PDA, NMDA evoked concentration-dependent depolarizations superimposed upon the basal cis-PDA-evoked depolarizations, the dose-response curve for which intercepted the control dose-response curve and was subsequently moved to the right compared with the control curve. 2AP5 shifted the NMDA dose-response curves to the right and Schild regression analysis gave a pKB of 5.0 with a slope of 1.00. 2AP5 also moved the cis-PDA dose-response-curve (apparent KB 3.1 X 10(-5) M) to the right and abolished the cis-PDA component of the NMDA + cis-DPA dose-response curve. These results are consistent with the predictions of drug-receptor theory for the interactions of a full agonist (NMDA), competitive antagonist (2AP5) and partial agonist (cis-PDA) and represent further evidence for a population of excitatory amino acid receptors for which NMDA is a selective agonist.
authors.forename: P L
authors.initials: PL
authors.lastname: Wheatley
authors.forename: K J
authors.initials: KJ
authors.lastname: Collins
mesh_terms: D015763:2-Amino-5-phosphonovalerate; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004594:Electrophysiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate; D010875:Pipecolic Acids / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D010875:Pipecolic Acids; D001224:Aspartic Acid; C029262:2,3-piperidinedicarboxylic acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D014633:Valine