Anions and cations as stimulators of liver adenylate cyclase

The effects of inorganic salts on adenylate cyclase activities were studied in rat liver homogenates, particulates, and purified membranes. Na+ salts of N-3, NO-2, S2O32-, SO42-, 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-beta, gamma-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 degree 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-beta, gama-imidodiphosphate (GMP-P(NH)P).