Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation

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Science  15 Aug 1975:
Vol. 189, Issue 4202, pp. 559-561
DOI: 10.1126/science.167439


Cyclic adenosine monophosphate (cyclic AMP) and 11 derivatives were applied to rat cerebellar Purkinje cells by iontophoresis. Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively. The ability of the 11 analogs to inhibit neuronal firing correlated ( r= + .78) with their reported potency in activating cyclic AMP-dependent protein kinase. These results extend previous studies, pointing to the mediation by cyclic AMP of the noradrenergic inhibition of Purkinje neurons, and provide new physiological evidence that protein phosphorylation is a major step in the action of cyclic AMP.