DIFFERENTIAL RESPONSIVENESS OF METABOTROPIC GLUTAMATE RECEPTORS COUPLED TO PHOSPHOINOSITIDE HYDROLYSIS TO AGONISTS IN VARIOUS BRAIN-AREAS OF THE ADULT-RAT

The effects of metabotropic glutamate receptor (mGluR) agonists on ino sitol phosphates (IF) accumulation were investigated in slices of the cerebral cortex, hippocampus, striatum and cerebellum of adult Sprague -Dawley rats. EC(50) values for 1S, 3R-1-aminocyclopentane-1,3-dicarbo xylic acid (ACPD) did not differ significantly between various brain a reas (range 10(-5) M), quisqualate was the most potent in all the brai n areas (range 10(-7)-10(-6) M), except the cerebellum (10(-5) M), ibo tenate was the most potent in the striatum (range 10(-6) M) and the le ast potent in the cerebral cortex and hippocampus (range 10(-4) M). Th e efficacy in the four brain areas showed the following trend of ranki ng order for ACPD and quisqualate: hippocampus > striatum > cerebral c ortex > cerebellum, and for ibotenate: hippocampus > cerebral cortex > striatum > cerebellum, although the observed differences reached the level of statistical significance only in the case of ACPD (hippocampu s and striatum vs cerebellum) and ibotenate (hippocampus vs cerebellum ). Go-incubation of the agonists at maximally effective concentrations in any pairwise combination resulted in no substantial additivity of IP accumulation. D,L-1-amino-3-phosphonopropionic acid (AP3) and D,L-2 -amino-4-phosphonobutyric acid (AP4) at 0.5 mM concentration antagoniz ed ACPD-induced IP accumulation by about 70 and 45%, respectively, wit hout differences between brain areas. On the other hand, the antagonis tic effects of L-serine-o-phosphate (SOP) at 1 mM concentration were t he highest in the hippocampus (75%) and the lowest in the cerebellum ( 25%). The comparative data indicate considerable regional receptor het erogeneity, in terms of different ratios of response to the agonists ( but not antagonists, except SOP). There is a robust responsiveness of mGluRs not only in the hippocampus and cerebral cortex, but also in th e striatum which exhibits the highest affinity to both quisqualate and ibotenate.