The regulation of basal and dopamine-sensitive adenylate cyclase by salts of monovalent cations in brain of the American cockroach, Periplaneta americana L.

Abstract

Production of cyclic AMP by cell-free preparations of cockroach brain is increased by dopamine and salts of monovalent cations. The effects of dopamine are GTP dependent with apparent plateaus in cyclic AMP production occurring at dopamine concentrations of between 1 and 10 μM and at 10 mM. Sodium chloride and potassium chloride elicit similar dose-dependent increases in cyclic AMP production ( K m = 15–20 mM) and choline chloride is slightly less effective ( K m = 29 mM). Sodium acetate has no effect of cyclic AMP production, sodium sulphate decreases cyclic AMP levels and sodium bromide enhances cyclic AMP production ( K m = 10 mM) in a manner similar to that of potassium chloride and sodium chloride. The cyclic AMP increase observed with sodium chloride is not dependent upon added GTP and doses of sodium chloride above 50 mM inhibit the stimulatory effects of 5′-guanylylimido-diphosphate. Forskolin enhances the effects of sodium chloride on cyclic AMP production by increasing maximal production and reducing the K m for sodium chloride. The dopamine-mediated (1.0 mM) increase in cyclic AMP production is reduced in the presence of sodium chloride, potassium chloride, choline chloride and sodium bromide with sodium chloride being most effective. Sodium acetate and sodium sulphate enhance the dopamine-mediated increase in cyclic AMP production. A fixed dose of sodium chloride (120 mM) shifts the dopamine dose-response curve to the right, thereby increasing the K m for the amine and reducing maximal stimulation. Inhibition of [ 3H]piflutixol ([ 3H]PIF) binding by dopamine is reduced in the presence of sodium chloride and lithium chloride but not by potassium chloride and choline chloride. The results indicate that the anionic moiety of the salt is most important in the stimulation of basal cyclic AMP production and in the inhibition of the dopamine-mediated increase in cyclic AMP. Halogens appear to be the most effective anions in mediating both effects. The ability of dopamine to inhibit [ 3H]PIF binding is reduced in the presence of the monovalent cations Na + and Li +.