Beta-2 adrenergic control of ornithine decarboxylase activity in brain regions of the developing rat.

Development of brain tissue is thought to be regulated, in part, by biogenic amines. We examined the role of noradrenergic stimulation in regulation of ornithine decarboxylase (ODC), an enzyme whose activity is obligatory for neuronal development and which has been used as a biochemical marker for cellular maturation. Intracisternal administration of adrenergic agonists produced a prompt increase in ODC in neonatal rat cerebellum, an effect mediated through beta-2 receptors: the rank order of activity was isoproterenol greater than epinephrine greater than norepinephrine greater than methoxamine; the effect could be blocked by propranolol but not phenoxybenzamine; and zinterol (a beta-2 selective agonist) was equipotent to isoproterenol whereas prenalterol (a beta-1 agonist) was ineffective. The elevation of ODC caused by adrenergic stimulation was cyclic AMP-dependent, as evidenced by: direct measurement of cyclic AMP levels after isoproterenol administration; comparisons of the dose-response curve for stimulation of cyclic AMP with that of ODC; examination of the time course of effect on the two variables; stimulation of ODC by administration of cyclic AMP analogs; demonstration of identical kinetic mechanisms for ODC stimulation by dibutyryl-cyclic AMP and isoproterenol; and potentiation of the actions of isoproterenol on both cyclic AMP and ODC by RO-201724, a specific inhibitor of phosphodiesterase. Examination of the ontogenetic pattern of phosphodiesterase.(ABSTRACT TRUNCATED AT 250 WORDS)

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Author Theodore Alan Slotkin Pharmacology & Cancer Biology