Abstract:
:Receptors for excitatory amino acids in the mammalian central nervous system are classified into three major subtypes, ones which prefer N-methyl-D-aspartate (NMDA), quisqualate (QA), or kainate (KA) as type agonists respectively. These receptors are considered to mediate fast postsynaptic potentials by activating ion channels directly (ionotropic type). Recently it was reported that exposure of mammalian brain cells to glutamate (Glu) or its analogues causes enhanced hydrolysis of inositol phospholipids, but it is not clear whether the enhanced hydrolysis is the cause or effect of physiological responses. Membrane depolarization or Ca2+ influx, which can result from Glu receptor activation, can induce enhanced hydrolysis of inositol phospholipids. We have characterized the functional properties of two types of excitatory amino-acid responses, those activated by QA (or Glu) and those activated by KA, induced in Xenopus oocytes injected with rat-brain messenger RNA. We report evidence for a new type of Glu receptor, which prefers QA as agonist, and which directly activates inositol phospholipid metabolism through interaction with GTP-binding regulatory proteins (Gi or Go), leading to the formation of inositol 1,4,5-trisphosphate (InsP3) and mobilization of intracellular Ca2+. This QA/Glu reaction is inhibited by islet-activating protein (IAP, pertussis toxin), but was not blocked by Joro spider toxin (JSTX), a specific blocker of traditional ionotropic QA/Glu receptors.
journal_name
Naturejournal_title
Natureauthors
Sugiyama H,Ito I,Hirono Cdoi
10.1038/325531a0subject
Has Abstractpub_date
1987-02-05 00:00:00pages
531-3issue
6104eissn
0028-0836issn
1476-4687journal_volume
325pub_type
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