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.