Abstract
The effects of norepinephrine, isoproterenol, serotonin, adenosine, veratridine, alpha and beta adrenergic antagonists, and combinations of these agents on the accumulation of cyclic [14C]AMP in cerebral cortical slices labeled during incubation with [14C]adenine has been ascertained with tissue obtained from control rats and from rats treated with intraventricular 2,4,3-trihydroxyphenethylamine (6-hydroxydopamine), 2,3,5-trihydroxyphenethylamine, 5,6-dihydroxytryptamine, or 5,7-dihydroxytryptamine. Treatment with 6-hydroxydopamine increased the accumulation of cyclic [14C]AMP elicited by norepinephrine, isoproterenol, and a combination of adenosine and norepinephrine. The responses to adenosine and veratridine were virtually unaffected. Both alpha and beta adrenergic receptor-mediated increases in cyclic 3',5'-AMP accumulation appeared to be potentiated by treatment with 6-hydroxydopamine. 2,3,5-Trihydroxyphenethylamine, although much more toxic than 6-hydroxydopamine, also enhanced the accumulation of cyclic [14C]AMP elicited by norepinephrine and isoproterenol. The dihydroxytryptamines caused no significant changes in cyclic [14C]AMP accumulation. The extent of accumulation of cyclic AMP elicited by a catecholamine in the presence of phosphodiesterase inhibitors, such as papaverine or isobutylmethylxanthine, was also significantly higher in slices from 6-hydroxydopamine-treated animals. Selective destruction of noradrenergic terminals in the cerebral cortex by trihydroxyphenethylamines thus appears to enhance the maximal accumulation of cyclic AMP elicited in slices by norepinephrine, primarily through mechanisms involving an increased rate of cyclic AMP formation from intracellular ATP rather than through a decrease in the rate of degradation of the cyclic nucleotide.
ACKNOWLEDGMENTS The authors gratefully thank Dr. Steven Victor, National Institutes of Health, for his generous advice and assistance related to the intraventricular injection of various drugs.
- Copyright ©, 1973, by Academic Press, Inc.
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