The addition of exogenous nicotinamide adenine dinucleotide (NAD) to isolated rat fat cells at concentrations between 1 and 10 μmol markedly inhibited the rise in cyclic AMP accumulation due to norepinephrine. Catabolism of NAD to adenosine did not account for the inhibitory effect since NAD was effective in the presence of adenosine deaminase. The bovine fraction V albumin in which fat cells were incubated contained a substantial amount of glycohydrolase which cleaved NAD to nicotinamide. Incubation of fat cells in albumin-free medium did not abolish the inhibitory effect of NAD, and under these conditions there was little degradation of NAD to nicotinamide during the first 10 min of incubation. Fat cells cleave NAD, in the medium to nicotinamide mononucleotide which does not inhibit cyclic AMP accumulation. NADH, NADP and nicotinic acid mononucleotide were less effective as inhibitors of cyclic AMP accumulation than NAD or deamido NAD. Ineffective as inhibitors were NADPH, nicotinamide mononucleotide, and 1-methyl nicotinamide. N′-methyl nicotinamide was as potent as nicotinamide while nicotinic acid was 100- to 500fold more effective than either compound as an inhibitor of cyclic AMP accumulation. Incubation of fat cells with 100 μM but not 10 μM NAD for 5 min resulted in a decrease in the subsequent accumulation of cyclic AMP by rat fat cell ghosts.
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Supported by USPHS research grant AM-10149 from the National Institute of Arthritis, Metabolism and Digestive Diseases
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Moreno, F.J., Shepherd, R.E. & Fain, J.N. Effect of NAD, nicotinamide and nicotinic acid on cyclic AMP accumulation by fat cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 306, 179–183 (1979). https://doi.org/10.1007/BF00498989
- Cyclic AMP metabolism
- Nicotinic acid
- Adenylate cyclase
- Nicotinamide adenine dinucleotide metabolism