Molecular Pharmacology, Vol 5, 572-579, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

The Effect of Structural Modifications of the Isoproterenol Molecule on the Stimulation of Deoxyribonucleic Acid Synthesis in Mouse Salivary Glands

¹ Fels Research Institute and Departments of Chemistry and Pathology, Temple University, Philadelphia, Pennsylvania 19140

A single injection of dl-isoproterenol causes, after a lag period of 20 hr, a marked stimulation of DNA synthesis and cell division in the salivary glands of rodents. The ability to stimulate DNA synthesis can be altered by modifications in the isoproterenol molecule as follows. (a) Replacement of the isopropyl group at the end of the side chain by a—CH₂CH₃ group results in an almost inactive molecule. In contrast, bulkier groups, such as—C(CH₃)₃, do not greatly alter the capacity to stimulate DNA synthesis. (b) Substituents on the - and -carbon atoms of the side chain have little or no effect on the ability of the parent molecule to stimulate DNA synthesis. (c) At least one of the two —OH groups on the phenyl ring is necessary for full activity. When both —OH groups are absent, the compound is totally inactive in stimulating DNA synthesis. (d) The d- and l-isomers are equally active in stimulating DNA synthesis.

The ability to stimulate DNA synthesis in the salivary gland is usually correlated with the capacity to stimulate -amylase secretion in the same organ and to cause glycogenolysis in the liver. However, there are a number of exceptions: for instance, (a) when both —OH groups of the phenyl rings are absent, the compound is still capable of eliciting salivary gland secretion; (b) d-isoproterenol, although quite effective in stimulating DNA synthesis, does not produce glycogenolysis in the liver.