guanosine-diphosphate and 2-amino-7-phosphonoheptanoic-acid

AMPA (EC50 = 1.0 x 10(-6) M) and NMDA (EC50 = 1.3 x 10(-4) M) trigger 45Ca2+ influx in 13-day chick embryonic retinal explants. This agonist-driven cationic flux is specifically inhibited by typical competitive antagonists, such as 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-7-phosphonoheptanoate (AP7), respectively. Guanine nucleotides, with different degrees of phosphorylation, namely 5'-GMP, guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) and 5'-guanylyl-imidodiphosphate (GppNHp), are also efficient blockers of 45Ca2+ influx. These results confirm the antagonistic behavior of guanine nucleotides towards ionotropic glutamate receptors and suggest a convenient experimental approach for screening of novel agonists and antagonists.

Topics: 2-Amino-5-phosphonovalerate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Biological Transport; Calcium; Calcium Radioisotopes; Chick Embryo; Excitatory Amino Acid Antagonists; Guanine Nucleotides; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Diphosphate; Guanosine Monophosphate; N-Methylaspartate; Organ Culture Techniques; Quinoxalines; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Retina; Thionucleotides

Long-term depression (LTD) is held relevant to memory and learning. Its induction is known to require postsynaptic calcium increases. However, the source of these calcium increases remains unclear. In visual cortex slices, LTD was induced by tetanization after blockade of N-methyl-D-aspartate (NMDA) and non-NMDA ionotropic glutamate receptors. LTD induced under this condition was prevented by an intracellular injection of each of the following drugs into the postsynaptic neuron: (i) guanosine 5'-[beta-thio]diphosphate, which competitively inhibits the binding of GTP to GTP-binding regulatory proteins; (ii) heparin, which antagonizes 1,4,5-inositol triphosphate binding; and (iii) calcium chelators. Moreover, LTD was induced without tetanization by applying quisqualate (10 microM), a metabotropic glutamate receptor agonist, but not another agonist, trans-aminocyclopentane-1,3-dicarboxylic acid (10 microM). Together, these results suggest that activation of 1,4,5-inositol trisphosphate-linked subtypes of metabotropic glutamate receptor is responsible for the increase in postsynaptic calcium concentration, which results in homosynaptic LTD.

Topics: 2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Amino Acids; Animals; Anticonvulsants; Bicuculline; Cyclopentanes; Evoked Potentials; gamma-Aminobutyric Acid; Guanosine Diphosphate; Heparin; In Vitro Techniques; Kinetics; Neuronal Plasticity; Neurons; Quinoxalines; Quisqualic Acid; Rats; Receptors, Glutamate; Synapses; Thionucleotides; Visual Cortex