Kainate and quisqualate effects on rat presynaptic cortical receptors are metabotropic and non-additive.
The effects of quisqualate and kainate on synaptosomal inositol phosphate (InsP) labelling, 45Ca influx and intrasynaptosomal free calcium ([Ca2+]i) were investigated. Each agonist caused a concentration-dependent increase in both [Ca2+]i and InsP labelling: quisqualate, however, produced significantly larger responses in both parameters and at lower EC50 values. Neither quisqualate or kainate significantly affected 45Ca influx into synaptosomes, indicating that the observed increases in [Ca2+]i were due to mobilisation from intracellular stores. The concentration-dependent increases in [Ca2+]i promoted by quisqualate and kainate were monophasic, whereas the increases in InsP formation fitted well to a biphasic curve. The EC50 values suggest that both kainate and quisqualate initially mobilise calcium from inositol 1,4,5-trisphosphate (Ins 1,4,5-P3)-sensitive stores and that the resultant increases in [Ca2+]i will, above a certain threshold, promote further increases in InsP production by stimulation of Ca(2+)-dependent phospholipase C. When saturating concentrations of kainate and quisqualate were used in combination, the effects on both InsP labelling and [Ca2+]i were not additive but were slightly higher than those produced by kainate alone: combined administration of the two agonists had no effect on 45Ca influx. These results suggest that kainate acts as a partial agonist at the presynaptic quisqualate metabotropic glutamatergic receptor.
Brammer
M J
MJ
Department of Neuroscience, Institute of Psychiatry, London, U.K.
Richmond
S
S
Xiang
J Z
JZ
Adamson
P
P
Hajimohammadreza
I
I
Silva
M A
MA
Campbell
I C
IC
D000818:Animals; D002132:Calcium Radioisotopes; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D016257:Fura-2; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D002132:Calcium Radioisotopes; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates; D007608:Kainic Acid; D016318:Quisqualic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D017981:Receptors, Neurotransmitter