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 characte rized biochemically and pharmacologically. Both ionotropic and metabot ropic receptor agonists stimulated [H-3] inositol phosphates accumulat ion in the following order of potency: QA>NMDA>L-glu>KA similar to QA> AMPA much greater than t-ACPD. QA showed a biphasic dose-response curv e (EC(50) = 0.07 and 53 mu M), suggesting interaction with two populat ions of receptors; L-glu was the most efficient agonist. Stimulation b y NMDA was blocked by CPP, AP5 and MK-801; that by AMPA and KA was inh ibited 100% by CNQX and DNQX, whereas the effect of QA was decreased b oth by CNQX and the metabotropic antagonist I-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-induce d [H-3]IPs accumulation was dependent on external Ca2+ and was not aff ected by nifedipine verapamil, or dantrolene; thapsigargin increased t he effect. Results suggest that EAA activate the PI pathway in Bergman n glia through ionotropic (NMDA and AMPA/KA) as well as metabotropic r eceptor subtypes (t-ACPD) which could act jointly influencing neurotra nsmission at the parallel fiber-Purkinje cell synapses in the cerebell um.