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

The effects of norepinephrine, histamine and adenosine, singly or in combinations, on the accumulation of adenosine 3',5'-monophosphate were examined in slices of cerebral cortex from strain 2 guinea pigs at 40 to 68 days of gestation. The response to histamine was 2-fold at 40 days, increased to 19-fold at 55 days and declined there after toward the adult value of 4-fold. The response to adenosine was first apparent at 44 days and developed rapidly to a maximum of about 40-fold at 55 days. The response to norepinephrine remained at about 2-fold throughout the entire period. Synergistic responses to combinations of pairs of agents all became visible at 42 days and the degree of synergism was maximal by 47 to 48 days of gestation. The pharmacological characteristics of responses in fetal tissue resembled those in adult tissue in that the effects of norepinephrine in the presence of either adenosine or histamine were mediated principally by alpha-adrenergic receptors and the responses to histamine were more effectively inhibited by H1 and H2 antagonists in the presence and absence of adenosine, respectively.