EXPRESSION AND COUPLING TO POLYPHOSPHOINOSITIDE HYDROLYSIS OF GROUP-IMETABOTROPIC GLUTAMATE RECEPTORS IN EARLY POSTNATAL AND ADULT-RAT BRAIN

We investigated the expression and coupling to the phospholipase C sig nal transduction pathway of metabotropic glutamate receptor (mGluR) su btypes by Western blot analysis and agonist-stimulated inositol monoph osphate formation in several brain regions of postnatal day 9 (P9) and adult rats. In the cerebral cortex, hippocampus, corpus striatum, olf actory bulb, cerebellum and hypothalamus, the expression level of mGlu R5 was greater at P9 than in adulthood. The mGluR5 signal was very low or absent in the adult cerebellum and hypothalamus. The expression of mGluR1a was slightly greater at P9 in the hypothalamus, hippocampus a nd olfactory bulb, whereas it substantially increased with age in the cerebellum, and did not change in the cerebral cortex and corpus stria tum. mGluR1b and -1c were nearly undetectable by Western blot analysis . The expression level of mGluR5, but not that of mGluR1a, was signifi cantly correlated with the extent of phosphoinositide hydrolysis stimu lated by mGluR agonists in slices prepared from these brain regions. T he mGluR antagonist cyclopropan[b]chromen-1a-carboxylic acid ethyleste r (CPCCOEt), potently antagonized responses mediated by mGluR1, but mu ch less potently those mediated by mGluR5a in recombinant cells. CPCCO Et, at a concentration which efficently blocks mGluR1 responses, did n ot substantially affect the polyphosphoinositide response in hippocamp al or cerebellar slices from newborn animals, and antagonized only a m inor component of the polyphosphoinositide response in adult hippocamp al slices. CPCCOEt, however, prevented the small stimulation of polyph osphoinositide hydrolysis by mGluR agonists in adult cerebellar slices . We conclude that (i) the efficient mGluR-mediated polyphosphoinositi de hydrolysis in g-day-old rats is mediated by mGluR5; (ii) the increa sed expression of mGluR1 in the adult cerebellum does not substitute f or the decline of mGluR5 expression in the ability to mediate polyphos phoinositide hydrolysis; and therefore (iii) mGluR1a might couple less efficiently than mGluR5 to polyphosphoinositide hydrolysis.