Anions and cations as stimulators of liver adenylate cyclase

The effects of inorganic salts on adenylate cyclase were studied in rat liver homogenates, particulates, and purified membranes. Na⁺ salts of N₃⁻, NO₂⁻, S₂O₃²⁻, and non-F⁻ halides stimulated homogenates by a maximum of 2–5-fold; half-maximal effects were seen at concentrations ranging from 90 mM (Na₂S₂O₃) to 410 mM (NaNO₂. NaIO₃ stimulated about 2-fold at relatively low salt concentrations (5–20 mM). Na⁺ salts were stimulatory using both ATP and the ATP analog 5′-adenylyl-β, γ-imidodiphosphate (AMP- P(NH)P) as enzyme substrate. The time courses of stimulation by NaCl and NaN₃ were linear to at least 10 min with any of the three tissue preparations. Although salt effects clearly varied with the different anions, the magnitude and dose-response of stimulation of homogenates by Cl⁻ salts were also dependent on the accompanying alkali cation (Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺). MgCl₂ at relatively high concentrations (50 mM) enhanced NaCl-stimulated activity in homogenates only slightly at relatively low concentrations of NaCl and not at high concentrations, suggesting a common mechanism of activation by Mg²⁺ and Na⁺ salts. NaCl- and NaN₃-stimulated activities were unstable in homogenates kept at 0°C for 4 h, falling to 35% and 50% of their respective baseline activities. The effects on homogenates and particulates of maximally stimulatory concentrations of NaCl and NaN₃ were further enhanced by GTP and the GTP analog 5′-guanylyl-β,γ-imidodiphosphate (GMP-P(NH)P).