Effects of insulin, adenosine, and prostaglandin on alpha-adrenergic-stimulated respiration in brown adipocytes

Abstract

The present study compared the effects of insulin, 2-chloroadenosine, and prostaglandin E2 as inhibitors of respiration in hamster brown adipocytes stimulated with either isoproterenol or phenylephrine. Addition of 2-chloroadenosine or prostaglandin E2 strongly antagonized isoproterenol-stimulated respiration; phenylephrine-stimulated respiration was also partially inhibited by 2-chloroadenosine and prostaglandin E2, but the extent of inhibition caused by these agents was not as great as when isoproterenol was used. Isoproterenol-stimulated respiration was inhibited by insulin, but phenylephrine-stimulated respiration was insensitive to the inhibitory effect of insulin. When brown adipocytes were pretreated with pertussis toxin, isoproterenol-stimulated respiration was enhanced, but phenylephrine-stimulated respiration was not significantly affected. The inhibitory effects of 2-chloroadenosine and prostaglandin E2 on isoproterenol-stimulated respiration were completely blocked by pertussis toxin, indicating that the mode of action of these inhibitory hormones was secondary to inhibition of adenylate cyclase and resultant inhibition of lipolysis. Prostaglandin E2 inhibition of phenylephrine-stimulated respiration was also abolished by pertussis toxin. In contrast, 2-chloroadenosine inhibition of phenylephrine-stimulated respiration persisted in adipocytes treated with pertussis toxin. These data suggest that phenylephrine stimulates respiration through a mechanism that is not altered by pertussis toxin and further that 2-chloroadenosine inhibition of isoproterenol- or phenylephrine-stimulated respiration can be dissociated.