Inhibition of adenylyl cyclase in rat striatal homogenates by combinations of dopamine and ferric iron compounds.

The adenylyl cyclase activity of homogenates of striatal tissue from rat brain has been used as a model to test the hypothesis that the products of the reaction of polyphenols with ferric iron compounds are toxic. Dopamine (DA), at levels that stimulate adenylyl cyclase, inhibited the activity in the presence of 2 mol of potassium ferricyanide (FC), methemoglobin or ferricytochrome c per mol of DA. Combinations of potassium ferrocyanide and DA were not inhibitory. Neither pyrocatechol nor hydroquinone stimulated the activity, but these polyphenols were inhibitory in the presence of FC. Tyramine, phosphorylated DA or phosphorylated pyrocatechol had no effect on the activity of the enzyme in the presence or absence of FC. Forskolin was unable to stimulate the adenylyl cyclase once the latter was inhibited by DA plus FC, and dithiothreitol could not reverse inhibition by DA plus FC. Incubation of DA with FC, in the absence of the homogenate, resulted in substances that were not inhibitory. These findings suggest that the polyphenols plus FC react to yield substances that inhibit the adenylyl cyclase by affecting the catalytic unit of the enzyme complex.