Molecular Pharmacology, Vol 20, 339-344, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Evidence for Alpha-Adrenergic Activation and Inactivation of Phosphorylase in Hamster Adipocytes

¹ Department of Physiology, College of Medicine and Dentistry of New Jersey, New Jersey School of Osteopathic Medicine, and Rutgers Medical School, Piscataway, New Jersey 08854

Exposure of hamster adipocytes to the selective beta-adrenergic agonist isoproterenol or to the selective alpha-adrenergic agonist methoxamine increased the percentage of phosphorylase a activity. When present together, the responses to methoxamine and isoproterenol were nearly additive. Of the alpha-adrenergic antagonists studied, prazosin was the most effective at blocking methoxamine activation of phosphorylase, followed by yohimbine and phenoxybenzamine. In contrast to the stimulatory action of methoxamine, clonidine (alpha₂-specific) did not activate phosphorylase. Incubation of cells with 3-isobutyl-1-methyl xanthine (IBMX) increased phosphorylase a activity to levels observed with isoproterenol. When cells were exposed to methoxamine or clonidine alone with IBMX, the stimulatory action of IBMX on phosphorylase a activity was partially prevented. The inhibitory effect of methoxamine was increased by prazosin and prevented by yohimbine. These results show, therefore, that alpha-receptor activation can both increase and decrease phosphorylase a activity. These results serve to strengthen the view that alpha-adrenergic inhibition of phosphorylase is mediated by alpha₂-receptors whereas activation of phosphorylase is mediated by alpha₁-receptors and that alpha-receptor can both increase and decrease phosphorylase a activity. We suggest that these oppositely directed responses result from two different subtypes of alpha-adrenergic receptors present upon hamster adipocytes.

Note:
ACKNOWLEDGMENTS The authors gratefully acknowledge Mr. Robert Gerzoff and Ms. Martha Propsner for technical assistance rendered and Ms. Marilyn Andril for preparation of the manuscript.