Guanine nucleotides block agonist-driven 45Ca2+ influx in chick embryo retinal explants.
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.
Burgos
J S
JS
Centro de Biologia Molecular (CSIC-UAM), Universidad Autónoma, Cantoblanco, Madrid, Spain.
Barat
A
A
Ramírez
G
G
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002642:Chick Embryo; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009924:Organ Culture Techniques; D011810:Quinoxalines / Q000494:pharmacology*; D018091:Receptors, AMPA / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D002132:Calcium Radioisotopes; D018691:Excitatory Amino Acid Antagonists; D006150:Guanine Nucleotides; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C056723:FG 9041; D016202:N-Methylaspartate; C023427:guanosine 5'-O-(2-thiodiphosphate); D015763:2-Amino-5-phosphonovalerate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D006157:Guanosine Monophosphate; C031231:2-amino-7-phosphonoheptanoic acid; D002118:Calcium