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Molecular Pharmacology, Vol 8, 521-530, Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics

Adenosine 3',5'-Monophosphate Concentrations and Isoproterenol-Induced Synthesis of Deoxyribonucleic Acid in Mouse Parotid Gland

A. GUIDOTTI 1, BENJAMIN WEISS 1, and E. COSTA 1

1 Laboratory of Preclinical Pharmacology, National Institute of Menthal Health, Saint Elizabeths Hospital, Washington, D. C. 20032

We studied the relationship between the concentration of adenosine 3',5'-monophosphate (cyclic 3',5'-AMP) and the rate of synthesis of DNA in the mouse parotid gland. Isoproterenol produced a dose-related increase in the concentration of cyclic 3',5'-AMP. This increase was maximal within 10 min and persisted longer than 2 hr. The rise of cyclic 3',5'-AMP in parotid gland was several times greater and longer-lasting than that seen in lung and heart, even though the concentration of isoproterenol in the parotid gland was lower than in lung and heart. Preliminary treatment of mice with aminophylline potentiated the isoproterenol-induced increase of cyclic 3',5'-AMP in parotid gland. Isoproterenol also increased the incorporation of [3H]thymidine into DNA and the total amount of DNA per gland as measured 28 hr after the injection. These increases were potentiated by prior treatment of the animals with aminophylline. In parotid gland we found a positive relationship between the concentration of cyclic 3',5'-AMP and the synthesis rate of DNA, whether isoproterenol was administered alone or in conjunction with aminophylline. Moreover, the increased concentration of cyclic 3',5'-AMP induced by these drugs preceded any changes in the synthesis of DNA. These results suggest that in parotid gland cyclic 3',5'-AMP may play a role in the acceleration of DNA synthesis elicited by isoproterenol.

Submitted on February 17, 1972




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