title: Eliminating the antilipolytic adenosine A1 receptor does not lead to compensatory changes in the antilipolytic actions of PGE2 and nicotinic acid.
abstract: OBJECTIVE
  We examined whether compensatory changes after adenosine A(1) receptor knockout [A(1)R (-/-)] eliminate the antilipolytic actions mediated by this receptor.
  
  
  METHODS
  Lipolysis experiments were performed on adipocytes prepared from the wild type A(1)R (+/+), A(1)R (-/-) and heterozygous mice. Gene expression was assayed with cDNA microarray technique and real-time PCR; protein expression with immunoblotting.
  
  
  RESULTS
  The A(1)R was the only adenosine receptor involved in lipolysis. The effects of adenosine deaminase and 2-chloroadenosine were abolished in A(1)R (-/-) mice. The IC(50) value of 2-chloroadenosine doubled from 16.6 to 33.6 nm when half of the A(1)Rs were eliminated. Adrenergic alpha(2) agonists had no effects on lipolysis. Prostaglandin E(2) (PGE(2)) inhibited lipolysis with an IC(50) value of 5.8 nm (4.7-7.2 nm) in the A(1)R (+/+) mice and 10.6 nm (9.0-12.6 nm) in the A(1)R (-/-) mice. Nicotinic acid inhibited lipolysis with an IC(50) value of 0.30 microm (0.19-0.46 microm) in the A(1)R (+/+) mice and 0.24 microm (0.16-0.37 microm) in the A(1)R (-/-) mice. G(i)alpha(1) mRNA was significantly up-regulated in adipose tissue from A(1)R (-/-) mice. However, immunoblotting showed that G(ialpha1) was not up-regulated at the protein level.
  
  
  CONCLUSIONS
  The A(1)R mediates the antilipolytic actions of adenosine. Deletion of the A(1)R in mice does not result in compensatory increases in G-protein-mediated antilipolytic actions of PGE(2) or nicotinic acid.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. stina.m.johansson@ki.se
authors.forename: S M
authors.initials: SM
authors.lastname: Johansson
authors.forename: J-N
authors.initials: JN
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Lindgren
authors.forename: B B
authors.initials: BB
authors.lastname: Fredholm
mesh_terms: D000241:Adenosine / Q000502:physiology; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D015232:Dinoprostone / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009525:Niacin / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000235:genetics / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018076:DNA, Complementary; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D043682:Receptor, Adenosine A1; D043562:Receptors, G-Protein-Coupled; D009525:Niacin; D000241:Adenosine; D015232:Dinoprostone