cyclic-gmp and methylazoxymethanol

Recent immunocytochemical studies of cerebellar nitric oxide synthase (NOS) and cGMP have aided dramatically in defining possible cellular sources of cGMP generation in the signal transduction cascade evoked by excitatory amino acids in the cerebellum. Using a mouse mutant deficient in cerebellar Purkinje cells ("nervous" mouse) and chemical lesions of cerebellar neurons with methylazoxymethanol (MAM), we have examined in vivo generation of cGMP to determine the roles of different cerebellar neuronal populations. In the case of "nervous" mice, our data indicate that cerebellar Purkinje cells are not required for NMDA-dependent increases in cGMP in the cerebellum. In marked contrast, MAM lesions which reduce granule but not Golgi cells in the granule cell layer and reduce basket and stellate cells in the molecular layer, dramatically reduced the ability of NMDA to increase cerebellar cGMP. These data support immunocytochemical data of cerebellar NOS pools and indicate the importance of granule, basket and possibly stellate cells in the generation of nitric oxide, which in turn activates guanylate cyclase, in a diversity of cells, to increase cerebellar cGMP levels.

Topics: Amino Acid Oxidoreductases; Amino Acids; Animals; Cerebellum; Cyclic GMP; Cytoplasmic Granules; Female; Golgi Apparatus; Harmaline; Immunohistochemistry; Methylazoxymethanol Acetate; Mice; Mice, Neurologic Mutants; N-Methylaspartate; Neurons; Nitric Oxide Synthase; Pregnancy; Purkinje Cells