Interactions between adenosine and alpha 1-adrenergic agonists in regulation of respiration in hamster brown...

Respiration in brown adipocytes can be increased by beta-adrenergic receptor agonists or by alpha 1-adrenergic receptor agonists (phenylephrine and norepinephrine). Previous studies have shown that beta receptor-stimulated respiration is inhibited by adenosine and that enzymatic removal of adenosine produced by fat cells under normal incubation conditions enhances the respiratory response to beta receptor activation. The present experiments were performed to determine the effect of adenosine on the respiratory response elicited by agonists of alpha 1 receptors. The alpha-adrenergic agonists phenylephrine and norepinephrine (in the presence of the beta-adrenergic antagonist propranolol) stimulated respiration and the respiratory response to each agent was enhanced when endogenous adenosine was removed with adenosine deaminase. Addition of hydrolysis-resistant analogues of adenosine inhibited phenylephrine-stimulated respiration, and, since N6-phenylisopropyladenosine was more effective than was 5'-N-ethylcarboxamidoadenosine, we conclude that an A1 receptor is involved. In contrast, the P site agonist 2',5'-dideoxyadenosine did not inhibit phenylephrine-stimulated respiration but did cause some inhibition of isoproterenol-stimulated respiration. These results suggest that adenosine, acting via A1 receptors, modulates alpha 1-adrenergic effects on thermogenesis in brown fat cells, an action that is analogous to its inhibition of beta-adrenergic receptor-stimulated thermogenesis.