The Influence of Chemical Agents on the Accumulation of Adenosine 3',5'-Phosphate in Slices of Rabbit Cerebellum

Abstract

Incubation of slices of rabbit cerebellum with norepinephrine for a few minutes resulted in large increases in the tissue content of adenosine 3',5'-phosphate. Exposure of slices to norepinephrine for more than 6 min led to a progressive disappearance of this nucleotide. Theophylline, a known inhibitor of cyclic-3',5'-ribonucleotide phosphodiesterase, had relatively little effect by itself upon the slice content of adenosine 3',5'-phosphate, but potentiated the effects of norepinephrine severalfold. In a survey of substances known to occur in the central nervous system, histamine, and to a lesser extent serotonin, were observed to produce effects similar to those of norepinephrine. The effects of histamine and norepinephrine were additive; phenoxybenzamine and diphenhydramine were observed to inhibit the effects of histamine at concentrations having relatively little influence on the action of norepinephrine while dichloroisoproterenol specifically prevented the effects of norepinephrine. Prolonged exposure of slices to norepinephrine desensitized slices to the readdition of norepinephrine, but not to histamine and vice versa. ACKNOWLEDGMENTS This work was supported in part by Grants AM-06141, NB-05716, and GM-661 from the U.S. Public Health Service. The authors also wish to acknowledge the skillful technical assistance of Mrs. Arleen Maxwell Haley and Mr. George Thorne in carrying out this work.