Molecular Pharmacology, Vol 20, 382-386, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Isoproterenol Stimulation of Ornithine Decarboxylase Blocked by Propranolol during Ontogeny of the Murine Heart

¹ Departments of Pharmacology and Internal Medicine, University of Arizona Health Sciences Center, Tucson, Arizona 85724

Fluctuations in the activity of fetal mouse heart ornithine decarboxylase (ODC) are positively correlated to growth rate. ODC activity was maximal (27 pmoles/min/mg of protein) at 13 days of embryogenesis, the earliest time that hearts could be dissected. Stimulation of fetal cardiac ODC activity was used as an index of cardiac responsiveness to adrenergic stimulation. The ability of either maternally injected or fetally injected isoproterenol to stimulate an increase in fetal heart ODC activity in embryos close to term was concentration-dependent. The beta-adrenergic stimulant, 10 mg/kg maternally or 2 mg/kg fetally, promoted a maximal response (300-400%). Maternal injections were used routinely, therefore, for ease of experimentation. The development of the fetal heart trophic response to beta-receptor agonists was examined after maternal injections of 2 or 10 mg/kg of isoproterenol from 13 to 21 days of gestation. Isoproterenol promoted an increase in myocardial ODC activity at all times monitored during fetal development. The highest drug-stimulated activity, 57 pmoles/min/mg of protein, occurred at 16-17 days of gestation. After this, the absolute specific enzyme activity achieved after isoproterenol declined, although the magnitude of the response remained at 2.5- to 3-fold above control until birth. The stimulation was blocked by propranolol (10 mg/kg s.c.). The maximal in vivo coupling of the beta-receptor to murine ODC activity, apparent from Day 13 of gestation, precedes the development of its in vitro coupling to the chronotropic response, first apparent after 17 days.

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ACKNOWLEDGMENTS We wish to acknowledge the technical assistance of Scott Ruth, Eleanor Fairbanks, Joanne Finch, and Mary Herber.