The effect of the divalent cations Mg2+ and Mn2+ on adenylate cyclase activity in white and brown adipose tissue of lean and obese (ob/ob) mice.
The divalent cations Mg2+ and Mn2+ in excess of the concentrations required to complex with ATP (excess Mg2+ or Mn2+) modulate the activity of adenylate cyclase. As a substrate, Mn X ATP was at least as effective as Mg X ATP in supporting adenylate cyclase activity in white and brown adipose tissue membranes. Both excess Mg2+ and Mn2+ had quantitatively different effects on the enzyme of lean and ob/ob mice and qualitatively different effects in white and brown adipose tissue. In white adipocyte membranes excess Mg2+ increase basal activity, as well as activity owing to guanylylimidodiphosphate (Gpp(NH)p) (with or without isoproterenol) and NaF. Maximal activation by Gpp(NH)p + isoproterenol required a higher concentration of Mg2+ in tissue from ob/ob than lean mice. Excess Mn2+ prevented the activation of the enzyme by Gpp(NH)p or Gpp(NH)p + isoproterenol in a dose-dependent manner. Mn2+ inhibited even in the presence of maximally effective Mg2+ concentrations. The enzyme of the ob/ob mouse membrane required a significantly higher dose of Mn2+ to achieve 50% inhibition. In brown adipose tissue, specific activities of the isoproterenol + Gpp(NH)p and NaF stimulated enzyme were significantly lower in the obese mice under all conditions studied. Except that NaF-stimulated activity was increased significantly more in the membranes of lean mice by the combination of Mg2+ + Mn2+, these cations did not produce significantly different dose-dependent effects in membranes from lean and ob/ob mice. Maximal activation occurred at lower concentrations MgCl2 (3-5 versus 10-20 mM) and required higher concentrations of MnCl2 (3-5 versus 1 mM) in brown than in white adipose tissue membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000201:enzymology*; D002001:Adipose Tissue, Brown / Q000201:enzymology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese
D006165:Guanylyl Imidodiphosphate; D008345:Manganese; D000262:Adenylyl Cyclases; D008274:Magnesium; D007545:Isoproterenol