Cellular Origins of Cyclic GMP Responses to Excitatory Amino Acid Receptor Agonists in Rat Cerebellum In Vitro

Abstract: Incubated slices and freshly dissociated cells from 8‐day‐old rat cerebellum were used to try to identify the cells that participate in the large increases in cyclic GMP levels that follow activation of excitatory amino acid receptors in this tissue. In the slices, cyclic GMP responses to L‐gluta‐mate and related excitants were unaffected by tetrodotoxin and could be replicated by the guanylate cyclase activator nitroprusside. Nitroprusside and the receptor agonists appeared to activate the same pool of the enzyme. Prior destruction of neuroblasts, deep nuclei, or Golgi neurones did not cause loss of responses to L‐glutamate. If granule cells were rendered necrotic, however, the cyclic GMP responses to all excitants tested were reduced by ≧ 90%. Substantial losses of responses to veratridine and high K+ levels also occurred, but the nitroprusside‐induced elevations were unaffected. In dissociated cell suspensions, the magnitude of responses to receptor agonists, but not those to nitroprusside, was markedly dependent on cell concentration. Responses to L‐glutamate were the same in cell suspensions that were Purkinje cell depleted and Purkinje cell enriched. It is concluded that granule cells are primarily involved in the cyclic GMP responses to excitatory amino acids but that the cyclic GMP accumulations occur elsewhere, probably in glial cells.