Inhibition of adenosine cyclic 3', 5'-monophosphate accumulation in fat cells by adenosine, N6-(phenylisopropyl) adenosine, and related compounds.

The hypothesis that adenosine may serve as a physiologica1 feedback regulator of adenylate cyclase in rat white fat cells was examined. Adenosine (0.2 µM), when added to incubated fat cells, caused 50% inhibition of the increase in adenosine cyclic 39,59-monophosphate accumulation due to 1.5 µM norepinephrine in the presence and absence of methylxanthines. The onset of adenosine inhibition was rapid and, if added 1 min after activators of adenylate cyclase, it reduced cyclic AMP accumulation during the next minute. Adenosine 59-monophosphate and adenosine 59-triphosphate were less effective than adenosine as inhibitors of cyclic AMP accumulation. Of a variety of nucleosides only N 6 -(phenylisopropyl)adenosine was more effective than adenosine in inhibiting cyclic AMP accumulation. Under conditions in which adenosine markedly reduced the small increase in cyclic AMP accumulation due to norepinephrine alone, it did not reduce lipolysis. In contrast, insulin reduced lipolysis but had a smaller effect on cyclic AMP accumulation. Adenosine inhibited lipolysis in the presence of insulin but produced no greater effect on cyclic AMP accumulation than was seen with adenosine alone. Drugs such as dipyridamole or papaverine did not affect cyclic AMP accumulation due to norepinephrine or block the inhibitory action of adenosine. Inhibition of cyclic AMP accumulation by adenosine was demonstrable also when cells were incubated in calcium-free buffer containing 0.25 mM ethylene glycol bis(β-aminoethyl ether)- N,N 9-tetraacetic acid. The addition of adenosine deaminase to incubated fat cells increased basal lipolysis and cyclic AMP and potentiated the norepinephrine-induced increase in cyclic AMP. The present results suggest that adenosine or related compounds may serve a physiologically important function as feedback regulators of adenylate cyclase.

• Publication year

  1973

• Venue

  Molecular Pharmacology

• Publication date

  1973-09-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0026-895x(25)13979-5PMID 4363014
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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