Accumulation of adenosine 3',5'-monophosphate in slices of rat cerebral cortex induced by alpha-adrenergic agonists. I. Responses to methoxamine and norepinephrine in adult and neonatal tissue.

The effects of adrenergic agonists and adenosine on the accumulation of adenosine 3',5'-monophosphate (cyclic AMP) were examined in cerebral cortical slices from adult and neonatal rats. Methoxamine (10 to 100 microM) produced up to a two-fold increase in tissue from adult animals only in the presence of optimal concentrations of adenosine (40 to 100 microM), but had no effect in neonatal tissue. Such responses were inhibited more readily by prazosin than by yohimbine, but the reverse was true for responses to norepinephrine; when tested without the addition of adenosine, however, responses to norepinephrine were somewhat more sensitive to prazosin. Under the latter conditions, norepinephrine induced about twice as much increase in cyclic AMP as did isoproterenol in adult tissue. While always prevented by alpha-adrenergic antagonists, the greater efficacy of norepinephrine was eliminated by methylxanthines only in some instances, but never in tissue from animals known to be less than 60 days of age. At 11 to 15 days of age, responses to norepinephrine were more than fourfold those to isoproterenol, even in the presence of methylxanthines, and were completely suppressed by propranolol. Responses to isoproterenol were enhanced when tested in the presence of adenosine, especially in neonatal tissue. The results suggest that both endogenous adenosine and age-related phenomena may account for some of the discrepancies among earlier studies. Moreover, they indicate that several populations of alpha-adrenergic receptors may be involved in responses to adrenergic agonists in rat cerebral cortical tissue.