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Molecular Pharmacology, Vol 7, 155-162, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Adenosine Cyclic 3',5'-Phosphate Formation in Cerebral Cortical Slices

Interaction among Norepinephrine, Histamine, Serotonin

M. HUANG 1, H. SHIMIZU 1, and J. DALY 1

1 National Institute of Arthritis and Metabolic Diseases, National Institutes of Health, Bethesda, Maryland 20014

Depolarizing agents (K+, ouabain, veratridine, and batrachotoxin), biogenic amines (norepinephrine, histamine, and serotonin), and adenosine cause accumulation of 14C-labeled adenosine cyclic 3',5'-phosphate (cyclic AMP) in cerebral cortical slices that have been labeled in a prior incubation with adenine-14C. The combined effect of supra maximal concentrations of depolarizing agents or adenosine with the biogenic amines is more than additive. The combined effect of supramaximal concentrations of norepinephrine and histamine or of serotonin and histamine is also more than additive. The data obtained are compatible with the existence of compartmentalized pools of adenine nucleotides serving as precursors for cyclic AMP and suggest that these pools are regulated in a synergistic manner by separate "receptors" for adenosine, histamine, and either norepinephrine or serotonin.

Note:
ACKNOWLEDGMENT The authors acknowledge the excellent technical assistance of Mrs. Marcia Phyillaier.

Submitted on October 3, 1970




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Science, April 12, 1974; 184(4133): 175 - 177.
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