The study by David S. Bredt and Solomon H. Snyder investigates the role of nitric oxide (NO) in mediating the enhancement of cyclic guanosine monophosphate (cGMP) levels in the cerebellum. They demonstrate that glutamate and related amino acids, such as N-methyl-D-aspartate (NMDA), significantly stimulate the conversion of arginine to citrulline and cGMP in cerebellar slices. Nω-monomethyl-L-arginine (MeArg), a potent inhibitor of arginine-to-citrulline conversion, blocks this stimulation, and arginine competitively reverses the effects of MeArg. Hemoglobin, which binds NO, prevents the stimulation by NMDA of cGMP levels, while superoxide dismutase, which increases NO levels, enhances cGMP formation. These findings confirm that NO mediates the stimulation of cGMP formation by glutamate. The study also suggests that Purkinje cells, which have high levels of cGMP and guanylate cyclase, are likely the primary site where glutamate receptors regulate cGMP levels.The study by David S. Bredt and Solomon H. Snyder investigates the role of nitric oxide (NO) in mediating the enhancement of cyclic guanosine monophosphate (cGMP) levels in the cerebellum. They demonstrate that glutamate and related amino acids, such as N-methyl-D-aspartate (NMDA), significantly stimulate the conversion of arginine to citrulline and cGMP in cerebellar slices. Nω-monomethyl-L-arginine (MeArg), a potent inhibitor of arginine-to-citrulline conversion, blocks this stimulation, and arginine competitively reverses the effects of MeArg. Hemoglobin, which binds NO, prevents the stimulation by NMDA of cGMP levels, while superoxide dismutase, which increases NO levels, enhances cGMP formation. These findings confirm that NO mediates the stimulation of cGMP formation by glutamate. The study also suggests that Purkinje cells, which have high levels of cGMP and guanylate cyclase, are likely the primary site where glutamate receptors regulate cGMP levels.