Phosphatidic acid and phosphatidylinositol labelling in adipose tissue. The role of endogenously formed adenosine.
Incorporation of [32P]Pi into phosphatidic acid and phosphatidylinositol of hamster epididymal adipocytes was partially inhibited by 3-isobutyl-1-methylxanthine. This effect of 3-isobutyl-1-methylxanthine was antagonized by isopropyl-N6-phenyladenosine but not by 2',5'-dideoxyadenosine, prostaglandin E1 or clonidine. N6-Phenylisopropyladenosine did not affect incorporation of [32P]Pi into phosphatidic acid or phosphatidylinositol when 3-isobutyl-1-methylxanthine was not present. In contrast with 3-isobutyl-1-methylxanthine inhibition of [32P]Pi incorporation into phospholipids, which was blocked only by N6-phenylisopropyladenosine, accelerated lipolysis was blocked by prostaglandin E1, clonidine and 2',5'-dideoxyadenosine as well as by N6-phenylisopropyladenosine. Phospholipid labelling was also decreased in the presence of adenosine deaminase, but not in the presence of isoprenaline (isoproterenol). The stimulatory effect of N6-phenylisopropyladenosine on [32P]Pi incorporation into phospholipids in cells exposed to 3-isobutyl-1-methylxanthine was evident as soon as 3 min after addition of the adenosine analogue and maximum 10 min after its addition. As observed by others, [32P]Pi incorporation into phospholipids was increased by the alpha 1-selective agonist methoxamine. The stimulatory effect of methoxamine occurred with a time course similar to that of N6-phenylisopropyladenosine and was present at nearly equal magnitude in the absence or presence of 3-isobutyl-1-methylxanthine. The inhibitory effects of 3-isobutyl-1-methylxanthine and adenosine deaminase on phospholipid labelling are attributed to blockade of the action, or to the enzymic removal, of adenosine formed in and released from the fat-cells during their incubation. Supporting this view is the selective reversal of the actions of 3-isobutyl-1-methylxanthine and of adenosine deaminase by N6-phenylisopropyladenosine. These findings suggest an important role for endogenous adenosine in regulation of phospholipid turnover in adipocytes.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006224:Cricetinae; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008647:Mesocricetus; D008729:Methoxamine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D010716:Phosphatidylinositols; D010743:Phospholipids; D000243:Adenosine Deaminase; D008729:Methoxamine; D000241:Adenosine; D007545:Isoproterenol; D003000:Clonidine; D015056:1-Methyl-3-isobutylxanthine