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Inhibition by Fluoride Ion of Hormonal Activation of Fat Cell Adenylate Cyclase

From the ¹ From the Section on Membrane Regulation, National Institute of Arthritis, Metabolism and Digestive Diseases, Bethesda, Maryland 20014

The adenylate cyclase system in a plasma membrane-rich fraction termed "ghosts" from rat adipocytes is activated by epinephrine, adrenocorticotropic hormone, glucagon, and secretin, and is also stimulated in the presence of fluoride ion. Studies of the temperature dependency of activation by these agents showed that whereas hormonal activation occurs down to 10°, activation by fluoride ion is minimal below 25°. When the enzyme system is incubated at temperatures below 25° with combinations of fluoride and each of the hormones, no hormonal activation is observed. At higher temperatures, enhanced activity observed in the presence of combinations of fluoride and hormones is probably due to fluoride alone. Thus fluoride abolishes hormonal activation of the adenylate cyclase system. The inhibitory effect of fluoride ion is independent of the concentration of the hormone. The inhibitory effect is also independent of the concentration of either ATP or magnesium ion in the assay system. The concentration dependency of the inhibitory effect is similar to that required for fluoride activation of the system. These observations provide the first evidence that fluoride exerts some effect on a process related to hormone action on adenylate cyclase. It is suggested that fluoride acts at some point on the pathway by which hormonal interaction with the receptor leads to an increase in the catalytic activity of the enzyme. This process may involve the "coupling" between the receptor and catalytic components of this complex enzyme system.

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