Effects of adenosine A1 receptor antagonism on lipogenesis and lipolysis in isolated rat adipocytes.
Adenosine is secreted from adipocytes, binds to adenosine A(1) receptor and modulates various functions of these cells. In the present study, the effects of an adenosine A(1) receptor antagonist (DPCPX; 0.01, 0.1 and 1 microM) on lipogenesis, glucose transport, lipolysis and the antilipolytic action of insulin were tested in rat adipocytes. DPCPX had a very weak effect on lipogenesis and did not significantly affect glucose uptake. In adipocytes incubated with 1 microM DPCPX, lipolysis increased. This effect was blunted by insulin and by a direct inhibitor of protein kinase A. Moreover, 0.1 microM DPCPX substantially enhanced the lipolytic response to epinephrine and increased cAMP in adipocytes. However, DPCPX was ineffective when lipolysis was stimulated by direct activation of protein kinase A. Adipocyte exposure to epinephrine and insulin with or without 0.1 microM DPCPX demonstrated that this antagonist increased the release of glycerol. However, despite the presence of DPCPX, insulin was able to reduce lipolysis. It is concluded that DPCPX had a weak effect on lipogenesis, whereas lipolysis was significantly affected. The partial antagonism of adenosine A(1) receptor increased lipolysis in cells incubated with epinephrine alone and epinephrine with insulin due to the synergistic action of 0.1 microM DPCPX and epinephrine.
Szkudelski
T
T
Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland. tszkudel@jay.au.poznan.pl
Szkudelska
K
K
Nogowski
L
L
D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D050155:Lipogenesis / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D014970:Xanthines / Q000494:pharmacology*
D058916:Adenosine A1 Receptor Antagonists; D007328:Insulin; D047428:Protein Kinase Inhibitors; D043682:Receptor, Adenosine A1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose; D000241:Adenosine; D005990:Glycerol; D004837:Epinephrine