Reverse transcription polymerase chain reaction revealed expression of mRNAs for particular receptors for the central neurotransmitter L-glutamic acid (Glu) in primary cultures of rat calvarial osteoblastic cells under premature to mature states according to the duration of days in vitro, These included metabotropic Glu receptors (mGluR) such as mGluR4 and mGluR8, in addition to several ionotropic Glu receptor subunits including NR1 and NR2D. Expression of mRNAs was not detected with other mGluR and NR2A-C subunits irrespective of the maturity of cultured cells. The agonist for group III mGluR L-(+)-2-amino-4-phosphonobutyric acid significantly inhibited the forskolin-induced accumulation of cAMP in premature osteoblasts, which occurred in a manner sensitive to prevention by the group III mGluR antagonist (RS)alpha -cyclopropyl-4-phosphonophenylglycine. These results suggest that Glu may at least in part play a role in mechanisms associated with cellular proliferation and/or differentiation through group III mGluR functionally expressed in rat calvarial osteoblastic cells.