Ontogeny of adenosine 3',5'-monophosphate metabolism in rabbit cerebral cortex. Development of responses to histamine, norepinephrine, adenosine, and glutamate.

The effects of norepinephrine (NE), histamine (HIST), glutamate, and adenosine, singly and in combinations, on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) in slices of rabbit cerebral cortex were examined using tissue from animals 4 days before to 38 days after birth. A response to NE became visible 2 days before birth and increased to a maximum at 7 days after birth before declining toward the small adult value during the second post-natal week. During this period NE was at least twice as efficacious as isoproterenol, and both alpha- and beta-adrenergic antagonists had prominent inhibitory effects. Responses to HIST were already apparent 4 days before birth and increased in an irregular fashion thereafter, sometimes exceeding the adult value during the second post-natal week. The response to adenosine was not visible until birth and gradually increased toward the adult value during the entire period examined. Synergistic responses to various combinations of the three agents were first detected at 2 to 4 days before birth. The degree of synergism was larger during the neonatal period than that found in adult tissue; no synergism between HIST and adenosine persisted in the adult. During the first post-natal week, L-glutamate produced very large increases of cyclic AMP accumulation in the presence of either adenosine or histamine plus theophylline; smaller but substantial responses occurred in combination with NE. Responses to glutamate declined progressively after about the tenth post-natal day.