The hydrolysis of phosphoinositides (PI) elicited in cerebellar granule cell cultures by agonists of metabolotropic glutamate receptors, glutmate and quisqualate, was enhanced when the cells were pretreated with concanavalin A (Con-A). A similar effect was produced by wheat germ agglutinin, but not by several other lectins tested. Con-A produced a dose-dependent effect (EC50 = 3 microM) and increased the efficacy but not the potency of the agonists. In contrast, Con-A failed to enhance PI hydrolysis evoked by N-methyl-D-aspartate, kainate, carbachol, the calcium ionophore A23187, or 50 mM K+. The Con-A stimulatory effect was prevented by simultaneous pretreatment with the agonists of ionotropic quisqualate receptors quisqualate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, but not by the antagonist 6-cyano-7-nitroquioxaline-2,3-dione (CNQX). CNQX, which did not inhibit quisqualate-stimulated PI hydrolysis in untreated cells, abolished the component of quisqualate response enhanced by Con-A pretreatment. The pretreatment with Con-A also increased the influx of 45Ca2+ in granule cells stimulated by quisqualate. This increase was inhibited by CNQX. Moreover, the potentiation of PI hydrolysis by Con-A, but not the response to quisqualate alone, was abolished in the absence of Ca2+ and Na+. Pretreatment of granule cells with pertussis toxin inhibited PI hydrolysis stimulated by the metabolotropic quisqualate receptor and the Con-A-potentiated response by the same percentage, but Ca2+ influx induced by quisqualate was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)