Excitatory amino acid (EAA)-induced production
of inositolphosphates (IPs) was studied in primary cultures
of chick retinal pigment epithelium (RPE) following in
vitro incorporation of [3H] myo-inositol.
Glutamic acid (L-glu) significantly increased [3H]-IPs
accumulation (215%). L-glu agonists stimulated [3H]IPs
accumulation in the following order of efficiency: N-methyl-D-aspartate
(NMDA) ≥ L-glu > quisqualate ≥ kainate > (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic
acid (ACPD). Stimulation was dependent on external Ca2+.
The NMDA-induced response was blocked by (+)-5-methyl-10,11-dihydro-5H-dibenzo-cyclohepten-5,10-imine
maleate (MK-801) and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic
acid (CPP) and was decreased by the L-Ca2+-channel
blockers verapamil and nifedipine as well as by dantrolene.
The metabotropic glutamate receptor (mGluR) antagonist
(+)-α-methyl-4-carboxyphenylglycine (+)MCPG inhibited
3,5-dihydroxyphenylglycine (DHPG) and ACPD-induced stimulation,
which demonstrates the presence in RPE of mGluRs 1 and/or
5, as well as NMDA receptors coupled directly, or through
the influx of external Ca2+, to phospholipase
C activation. L-glu agonists showed no effect either on
basal level of intracellular cyclic adenosine monophosphate,
nor on forskolin- or carbachol-induced stimulation of adenylyl
cyclase. Since L-glu is released from the retina upon illumination,
and receptors for this compound are present in RPE, the
activation of the inositide pathway could be involved in
the regulation of retina-RPE interaction, which is essential
for the visual process.