Excitatory amino acid receptors coupled to the phosphoinositide pathway in Bergmann glia.
Glutamate (L-glu) receptors coupled to phosphoinositide hydrolysis in primary cultures of Bergmann cells from chick cerebellum were characterized biochemically and pharmacologically. Both ionotropic and metabotropic receptor agonists stimulated [3H] inositol phosphates accumulation in the following order of potency: QA > NMDA > L-glu > KA approximately QA > AMPA > > t-ACPD. QA showed a biphasic dose-response curve (EC50 = 0.07 and 53 microM), suggesting interaction with two populations of receptors; L-glu was the most efficient agonist. Stimulation by NMDA was blocked by CPP, AP5 and MK-801; that by AMPA and KA was inhibited 100% by CNQX and DNQX, whereas the effect of QA was decreased both by CNQX and the metabotropic antagonist 4-CPG. Stimulation of PIP2 hydrolysis induced by metabotropic L-glu receptor agonist t-ACPD was blocked by 4-CPG but was only moderately inhibited by MCPG. EAA-induced [3H]IPs accumulation was dependent on external Ca2+ and was not affected by nifedipine verapamil, or dantrolene; thapsigargin increased the effect. Results suggest that EAA activate the PI pathway in Bergmann glia through ionotropic (NMDA and AMPA/KA) as well as metabotropic receptor subtypes (t-ACPD) which could act jointly influencing neurotransmission at the parallel fiber-Purkinje cell synapses in the cerebellum.
López-Colomé
A M
AM
Departamento de Neurociencias, U.N.A.M., México, D.F. México.
Ortega
A
A
Fragoso
G
G
Trueba
E
E
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006868:Hydrolysis; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D013268:Stimulation, Chemical
D015220:Calcium Channels; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D016318:Quisqualic Acid