Generation of inositol phosphates, cytosolic Ca²⁺ and secretion of noradrenaline in PC12 cells treated with glutamate

Glutamate transiently stimulated rat pheochromocytoma PC12 cells and caused an inositol trisphosphate formation and an increase in levels of Ca+ in the cytosol. The rank order of potency of glutamate greater than N-methyl-D-aspartate (NMDA) much greater than kainate = quisqualate is characteristic of an interaction with NMDA receptors. The effect of glutamate on inositol trisphosphate formation disappeared in a low Mg2+ buffer and was not blocked by DL-2-amino-5-phosphonovalerate, an antagonist for NMDA receptors coupled to ion channels. Although glutamate failed to stimulate noradrenaline secretion, glutamate enhanced the effect of bradykinin, but not of Ca ionophore A23187, or KCl. These results suggest the existence of metabotropic glutamate receptors, different from previously reported receptors, in PC12 cells.