Excitatory amino acid-induced formation of inositol phosphates in guinea-pig cerebral cortical slices: involvement of ionotropic or metabotropic receptors?
In cerebral cortical slices from the guinea-pig, quinoxalinedione derivatives antagonised the generation of 3H-inositol phosphates evoked by the excitatory amino acids quisqualate and DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid but were without effect on the trans-DL-1-amino-1,3-cyclopentanedicarboxylic acid and L-glutamate responses. Omission of calcium from the medium reduced the accumulation of 3H-inositol phosphates induced by incubation with trans-DL-1-amino-1,3-cyclopentanedicarboxylic acid (incubation for 45 min) by greater than 50%, whereas the responses to L-glutamate and the two other amino acid analogues were reduced by approximately 20%. Generation of inositol 1,4,5-trisphosphate over a 30-s period by treatment with quisqualate, trans-DL-1-amino-1,3-cyclopentane-dicarboxylic acid, KCl, and carbachol was abolished in the presence of nominally calcium-free medium. L-Glutamate induced a large, rapid increase in inositol 1,4,5-trisphosphate mass (more than three-fold), which was, however, unaffected by omission of calcium from the medium. These results indicate that of the excitatory amino acids tested, only L-glutamate may be classed as a metabotropic receptor agonist in guinea-pig cerebral cortical slices with respect to generation of inositol phosphates. The other agents appear to stimulate accumulation of inositol phosphates, at least in part through some mechanism requiring the presence of extracellular Ca2+, presumably Ca2+ entry.
Alexander
S P
SP
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, England.
Hill
S J
SJ
Kendall
D A
DA
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003515:Cycloleucine / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010069:Oxadiazoles / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D016318:Quisqualic Acid; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000596:Amino Acids; D005971:Glutamates; D010069:Oxadiazoles; D010080:Oxazoles; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D003515:Cycloleucine; D007051:Ibotenic Acid; D018698:Glutamic Acid; D011189:Potassium Chloride; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D015544:Inositol 1,4,5-Trisphosphate; D016318:Quisqualic Acid; D002217:Carbachol; D002122:Calcium Chloride